Current state-of-the-art review of nanotechnology-based therapeutics for viral pandemics: Special attention to COVID-19

Marjan Motiei; Lucian A. Lucia; Tomas Sáha; Petr Sáha

doi:10.1515/ntrev-2022-0515

Article Open Access

Current state-of-the-art review of nanotechnology-based therapeutics for viral pandemics: Special attention to COVID-19

Marjan Motiei , Lucian A. Lucia , Tomas Sáha and Petr Sáha

Published/Copyright: February 13, 2023

Published by

Become an author with De Gruyter Brill

Submit Manuscript Author Information

From the journal Nanotechnology Reviews Volume 12 Issue 1

Abstract

Over the past two centuries, most pandemics have been caused by zoonotic RNA viruses with high mutation, infection, and transmission rates. Due to the importance of understanding the viruses’ role in establishing the latest outbreak pandemics, we briefly discuss their etiology, symptomatology, and epidemiology and then pay close attention to the latest chronic communicable disease, SARS-CoV-2. To date, there are no generally proven effective techniques in the diagnosis, treatment, and spread strategy of viral diseases, so there is a profound need to discover efficient technologies to address these issues. Nanotechnology can be a promising approach for designing more functional and potent therapeutics against coronavirus disease 2019 (COVID-19) and other viral diseases. Moreover, this review intends to summarize examples of nanostructures that play a role in preventing, diagnosing, and treating COVID-19 and be a comprehensive and helpful review by covering notable and vital applications of nanotechnology-based strategies for improving health and environmental sanitation.

Graphical abstract

Nanotechnology is a promising approach for preventing, diagnosing, and treating COVID-19 and related viral diseases.

Keywords: viral pandemics; nanotechnology; prevention; diagnosis; treatment

Abbreviations

Alum: Aluminum hydroxide
ACE2: Angiotensin-converting enzyme II
CDs: Carbon dots
CNTs: Carbon nanotubes
CTD: Carboxy-terminal domain
CS: Chitosan
COVID-19: Coronavirus disease 2019
EWNS: Engineered water nanostructures
G: Graphene
GO: Graphene oxide
HA: Hemagglutinin
HSPG: Heparan sulfate proteoglycan
HEK: Human embryonic kidney
HIV: Human immunodeficiency virus
IPC: Infection prevention and control
IAV: Influenza A virus
IVM: Ivermectin
KGM: Konjac glucomannan
LFIA: Lateral flow immunoassay
LNPs: Lipid NPs
Mal: Maleimide
MERS-CoV: Middle east respiratory syndrome coronavirus
MWCNTs: Multi-walled carbon nanotubes
NP: Nanoparticle
NTD: Amino-terminal domain
HTCC: N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride
NA: Neuraminidase
ORFs: Open reading frames
PPE: Personal protective equipment
PF: Phenol-formaldehyde
PEG: Poly(ethylene glycol)
PEI: Poly(ethyleneimine)
PDMS: Poly(dimethylsiloxane)
PLA: Poly(lactic acid)
PLGA: Poly(lactic-co-glycolic)
PMMA: Poly(methylmethacrylate)
PP: Polypropylene
PS: Polystyrene
PVA: Poly(vinyl alcohol)
PVDF: Poly(vinylidene fluoride)
RBD: Receptor-binding domain
Rha(s): Rhamnolipids
RT-PCR: Reverse transcription polymerase chain reaction
SARS: Severe acute respiratory syndrome
SARS-CoV: Severe acute respiratory syndrome coronavirus
SA: Sialic acid
ssRNA: Single-stranded RNA
SERS: Surface-enhanced Raman scattering
TMB: Tetramethylbenzidine
UV: Ultraviolet
UTR: Untranslated region

1 Introduction

A pandemic is an epidemic in which the vector contagion spreads globally. Despite technological developments, pandemics have been prevalent during the last two centuries. Except for the sixth cholera pandemic (1910–1911) that originated by a bacterium (Vibrio cholera), most pandemics have been caused by zoonotic RNA viruses [1]. These RNA viruses demonstrate high pandemic potential owing to the lack of a proofreader. Therefore, they show higher mutation rates than the DNA varieties and are more adaptable to human infection and transmission. The other concerning situation is spreading through respiratory droplets, which transmit from person to person through close interactions [2]. According to Table 1, most of these pandemics are attributed to contagious respiratory illnesses induced by influenza viruses and coronaviruses, while the other is an acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) affecting the reproductive tract, the urinary tract, and the digestive tract (oral cavity, anus, and rectum). Herein, we briefly compare these three zoonotic RNA viruses epidemiologically and then focus on various strategies to prevent, diagnose, and treat the latest chronic communicable disease, which can also be applicable in other virus-induced diseases.

Table 1

Different virus pandemics that have spread globally and continue to this day (since 1918)

Pandemic	Virus	Years of activity	Country of origin	Animal vector	Global mortality rate (in millions)	Average mortality age
Spanish Flu	A/H1N1	1918–1920	Spain	Avian	50	Very young, elderly, and healthy young adults aged 20–40
Asian Flu	A/H2N2	1956–1958	China	Avian	1–2	School-age children and young adults aged 35–40
Hong Kong Flu	A/H3N2	1968–1970	Hong Kong	Avian	0.5–2	62–65
AIDS	HIV/AIDS	1981–Present	Democratic Republic of the Congo	Chimpanzee	36	Males about 50.8 years, and females about 49.7 years reported in 2013. http://www.cdc.gov/nchs/data_access/vitalstatsonline.htm.
Swine Flu	A/H1N1	2009–2010	Mexico	Pigs	0.148–0.249	37
COVID-19	SARS-CoV-2	2019–Present	China	Bats, pangolins?	5.7 through February 2022	0.02% in age of 20–49, 0.5% age of 50–69, and greater than 5.4% in age of more than 80

1.1 AIDS

The virus causing HIV belongs to the Retroviridae family with a diameter ∼100 nm. Two major types of HIV are: HIV-1 (the most common and responsible for over 95% of all infections) and HIV-2 (relatively uncommon and less infectious). The spherical HIV-1 virion contains two copies of (+)ssRNA genome and replicative enzymes surrounded by a membrane containing HIV-1 envelope glycoprotein (Figure 1a). This sole antigen is a homotrimeric protein post-translationally cleaved into gp41, the transmembrane domain that constitutes the protein’s fusion peptide, and gp120, a surface domain that mediates receptor binding [3]. The binding of HIV-1 envelope glycoprotein to the CD4⁺ T cells induces conformational changes in the glycoprotein and subsequent interaction with chemokine co-receptors such as CCR5 and CXCR4 to facilitate active transport processes. Afterwards, in the presence of enzymatic machinery, RNA transforms into DNA in the host cell’s cytoplasm and subsequently integrates into the cell genome. Consequently, chronic disease is a result of strong antibody responses, which can progress to AIDS [4,5].

Figure 1

Schematic representation showing the structure of: (a) HIV, (b) IAVs, and (c) SARS-CoV-2.

HIV transmission mechanism: Direct contact of the infected patient’s biofluids (i.e., blood, breast milk, male and female sexual fluids) with the specific mucosa or bloodstream of the other person lead to HIV-1 transmission [4]. Therefore, transmission mechanisms are categorized according to three routes: sexual, parenteral, and vertical. Sexual transmission occurs with a high concentration of HIV-1 in the genital tract with a higher transmission risk for females [6]. Parenteral transmission occurs after biofluids’ contact subcutaneously, intramuscularly, or intravenously [7]. Finally, vertical transmission is defined as mother-to-child-transmission, which occurs via three different routes, including utero, intrapartum, and breastfeeding [8].

HIV symptomatology: The symptoms appear as an acute infection within the first two months and chronic infection following the next six months. In the acute phase, infected people present swollen lymph nodes, fever, headache, rashes, and pains in the muscles, throat, and mouth. In the chronic phase, immunosuppression happens, and AIDS, with many life-threatening diseases, occurs in an untreated infection [4].

HIV therapeutics and treatment: A prima facie treatment goal is to limit viral transmission by reducing the viral load in biofluids. Therapeutic vaccination is the most cost-effective, non-invasive, promising strategy for long-lasting immunity [9]. Passive antibody administration, latency reversal agents, adjuvants, and immune modulators are known to enhance vaccine potency [10]. Histone deacetylase inhibitor romidepsin [11], two major categories of Integrase Inhibitors, and single drug molecule with dual inhibitor activity against integrase and reverse transcriptase are among a suite of promising therapeutics [8].

1.2 Influenza (Flu)

Influenza viruses with A, B, C, and D subtypes belong to the Orthomyxoviridae family. They possess ∼150–200 nm diameters with roughly spherical to pleomorphic and filamentous shapes. The envelope is a host-derived lipid bilayer, where the spikes are radiated outward [12]. They have seven or eight (−)ssRNA genome encoding structural and non-structural proteins. Influenza A viruses (IAVs) are the only ones with a pandemic potential (Table 1). IAVs have eight single-stranded viral RNA segments in separate viral ribonucleoprotein (RNP) complexes packaged into a single virus particle (Figure 1b). The structure of viral RNA plays an essential role in directing gene reassortment between human IAVs and animal reservoirs, which led to the emergence of pandemic subtypes [13]. There are different IVAs based on the rod-shaped spikes of hemagglutinin (HA) and mushroom-shaped spikes of neuraminidase (NA). HAs encoded by 1–16 genes and NAs encoded by 1–9 genes are involved in viral attachment and release, which happens at various pH and times during the virus life cycle [12]. Of the 144 total combinatorial possibilities, only four combinations of HAs and NAs (H1N1, H2N2, H3N2, and possibly H3N8) cause pandemics owing to partial or lacking immunity in the human genome [1].

Transmission mechanism: The most important routes of IVA transmission are via contact (i.e., direct, indirect, and droplet), air, or a combination. Direct contact occurs via direct physical contact between an infected patient and a susceptible host). Indirect contact occurs by passive transfer of IVA to a susceptible host via contaminated hands, instruments, or other intermediate objects. Large droplets (≥5 µm diameter) generated from the respiratory tract of a colonized individual is the other way of contact transmission. Finally, airborne transmission via aerosols can occur over airborne particles less than 5 µm or dust particles containing IVA [14].

Symptomatology: Typical upper respiratory tract infection symptoms include fever and chills, nonproductive cough, rhinitis, muscle pain, and sore throat. In most people, these symptoms, except cough and malaise, resolve after 3–7 days, which can continue for more than 2 weeks, primarily in elder and chronic lung infected individuals. In severe disease, otitis media, respiratory, cardiac, musculoskeletal, and neurologic complications may occur [15].

Influenza therapeutics and treatment: The main treatment goal reduction of the viral load by diminishing viral replication. The treatment is initiated by prescription of NA inhibitors (oseltamivir) plus fibrates (fenofibrate). Due to virus NA mutations, Fludase (a recombinant sialidase fusion protein), Nitazoxanide (a novel thiazolide that inhibits IVA replication), and Favipiravir may cover resistant influenza strains. Corticosteroids are the other common drug, which may not be ideal for influenza viral infections [16].

1.3 Severe acute respiratory syndrome (SARS)

The life-threatening respiratory infection, SARS, is driven by an important species of the Coronaviridae family, SARS-associated coronavirus. The four genera of these coronaviruses are alpha, beta, delta, and gamma [17]. While alpha and beta originate from mammals, in particular particularly bats, gamma and delta originate from pigs and birds [18]. The enveloped (+)ssRNA viruses encode structural and non-structural proteins. Proteins of the membrane, spike, envelope, and nucleocapsid are the four main structural proteins [1]. Among the seven subtypes that infect humans, alpha‐coronaviruses (i.e., HCoV-229E and HCoV-OC43) cause asymptomatic or mildly symptomatic infections [1,18]. Whereas beta-coronavirus subgenuses lead to diseases with varying degrees of infectious potential, including lower respiratory tract infection through HCoV-NL63 and HCoV-HKU1, severe pneumonia through SARS-CoV, middle east respiratory syndrome coronavirus (MERS-CoV), and finally SARS-CoV-2 [1].

Table 2 describes the epidemiological characteristics of SARS infections. Infectious bronchitis virus is a gamma-coronavirus that produces highly contagious disease in chickens, especially in the reproductive and upper respiratory tracts [17]. However, different delta-coronavirus species have not caused disease in wild birds; a sickness in farmed quail in Poland and psittacine proventricular dilatation disease in green-cheeked Amazon parrot are attributed to delta-coronavirus [19]. Herein, we focus on SARS-CoV-2 properties, transmission mechanisms, and symptomatologies.

Table 2

The epidemiological characteristics of SARS infections

	SARS-CoV epidemic	MERS-CoV epidemic	SARS-CoV-2 pandemic
Common symptoms	Influenza-like syndrome with dry cough, fever, malaise, body aches and pains, diarrhea	Cough, fever, breathlessness, and even gastrointestinal issues	Cough, fever, breathlessness, loss of taste or smell, potential gastrointestinal issues
Years	2002–2003	2015–present	2019–present
Potential animal reservoirs	Bats	Bats	Bats, pangolins
Intermediary hosts	Palm civets	Dromedary camels	Not identified yet
Origin	Guangdong province (China)	Jeddah (Saudi Arabia)	Wuhan (China)

1.3.1 SARS-CoV-2

This subgenus of beta-coronavirus shows a high sequence identity as a Bat beta-coronavirus [4,17]. The virion size is around 70−90 nm, whose complete genomic sequence shows a high genetic similarity with other subtypes inducing respiratory infections [4]. The genome is encapsulated by a protein-based capsid covered by a phospholipid bilayer membrane (Figure 1c). The membrane is essential for virus-cell fusion through the binding of the spike protein and cellular angiotensin-converting enzyme II (ACE2) of the target tissues (i.e., lung, cardiovascular system, intestine, and kidney) [20]. After releasing the viral genome containing 6–20 open reading frames (ORFs) into the host cytoplasm, ORF1a/b is translated into two structural and 16 non-structural proteins to assemble into replication–transcription complexes. The complexes within double-membrane vesicles synthesize sets of genomic and subgenomic RNAs that encode several structural and accessory proteins. The newly formed RNAs, nucleocapsid, and envelope proteins bud from the endoplasmic reticulum-Golgi apparatus and merge with the cell membrane to form new viral particles [4]. The viruses have demonstrated different mutations, especially on spike protein, which led to further variants with different transmission rates, reinfection risk, disease severity, and treatment [21]. This trimeric glycoprotein contains two domains of S1 and S2. The exposed S1 domain is in a more variable mode than the partially buried S2 domain. The main parts of S1 also include the receptor-binding domain (RBD), amino-terminal domain (NTD), and carboxy-terminal domain (CTD), which the RBD and the NTD show more variability than CTD [21]. The variability leads to many variants, as described in Table 3. According to the WHO, in April 2022, delta and omicron are categorized in variants of concern, and the others as variants of interest.

Table 3

Different SARS-CoV-2 mutations and variations along with their epidemiology

Variant	Lineage	Origin	Date	Mutations	Transmissibility	Severity	Ref.
Epsilon	B.1.427	California	March 2020	Spike mutations: RBD, NTD, CTD, signal peptide	18.6–24% more than the wild-type strains	No evidence	[22]
Epsilon	B.1.429	California	March 2020	Spike mutations: RBD, NTD, CTD, signal peptide	18.6–24% more than the wild-type strains	No evidence	[22]
Zeta	P.2 (B.1.1.28.2)	Brazil	April 2020	Spike mutations: RBD, CTD	Increase 23%	No evidence	[23]
Beta	B.1.351	South Africa	May 2020	Spike mutations: RBD, NTD deletion	50% more than the previously circulating variants	High	[24]
Alpha	B.1.1.7	UK	September 2020	Spike mutations: RBD, NTD deletions	Highest with a 50–100% reproduction rate	High with 50% increased mortality	[25,26]
Alpha	B.1.1.7	UK	September 2020	Non-spike mutations: nucleocapsid, p6:Δ106–108,	Highest with a 50–100% reproduction rate	High with 50% increased mortality	[25,26]
Delta	B.1.617.2	India	October 2020	Spike mutations: RBD, NTD, CTD, S2, proximal furin cleavage site	More than the alpha	High	[27,28]
Delta	B.1.617.2	India	October 2020	Non-spike mutations: orf3, orf7a, orf1a/b, and Nucleocapsid gene	More than the alpha	High	[27,28]
Kappa	B.1.167.1	India	October 2020	Spike mutations: RBD, NTD, S2, proximal furin cleavage site	High but less than delta	No evidence	[29]
Kappa	B.1.167.1	India	October 2020	Non-spike mutations: orf3, orf7a, orf1a/b, Nucleocapsid gene	High but less than delta	No evidence	[29]
Gamma	P.1 (B.1.1.28.1)	Brazil	November 2020	Spike mutations: RBD, Five NTD mutations	High	High	[30]
Iota	B.1.526	New York	November 2020	Spike mutations: RBD, NTD, CTD, signal peptide, Near the furin cleavage site	High	High	[31]
Iota	B.1.526	New York	November 2020	Non-spike mutations: T85I, L438P, 9 bp deletion Δ106-108, P323L, Q88H, Q57H, P199L and M234I	High	High	[31]
Eta	B.1.525	Nigeria	December 2020	Spike mutations: RBD	Lower than Alpha variant	High	[32]
Lambda	C.37	Peru	December 2020	Spike mutations: RBD, NTD deletion	No evidence	No evidence	[33]
Theta	P.3	Philippines	January 2021	Spike mutations: RBD, NTD deletion, CTD	High	No evidence	[34]
Mu	B.1.621	Colombia	January 2021	Spike protein: RBD, NTD, CTD, S2 region	High	No evidence	[35]
Omicron	B.1.1.529	Multiple countries	November 2021	Spike mutations: RBD, NTD, CTD, fusion peptide, heptad repeat 1, proximal to the S1/S2 cleavage site, S2 protein	High	Low	[36]

SARS-CoV-2 transmission mechanism: It may be transferred directly by human biofluids and indirectly by the environment (i.e., waters, foods, and many surfaces) [4,37]. The primary transmission methods are through aerosols with a particle diameter of <5 µm during respiration, vocalism, or the solid residual particles after the droplet vaporization [38]. There is no report on SARS-CoV-2 infection transmission via food, but it should be mentioned that CoVs may survive at 4°C up to 2–4 days on fresh food [39]. According to WHO, the risk of fecal transmission seems to be low. However, feces may be a reason of hands, water, food contaminations [40], and coronavirus disease 2019 (COVID-19) transmission through fecal–oral, fecal–fomite, or fecal–aerosol [41,42].

SARS-CoV-2 symptomatology: Most cases reveal mild symptoms such as fever, cough, dyspnea, diarrhea, and abdominal pain 2–14 days after exposure. Nonetheless, most severe cases show progressive respiratory failure and even death [4].

2 Nanotechnology for prevention, diagnosis, and treatment

Infection prevention and control (IPC) relies on a thorough understanding of the factors that affect transmission [43]. To implement IPC, nanotechnology is a discipline that offers scientific and practical approaches to the prevention, diagnosis, and treatment of infectious illnesses. In the case of prevention, nano-sized vaccines mimic the virus without any replicated genome, replaceable nanoporous membrane for N95 face masks, applying self-disinfecting nanocoatings for air filters, and using nano-disinfectants in the environment are examples of nanotechnology in the prevention of virus spread [44]. Nanodiagnostics also rely on combining nanoparticles (NPs) with target molecules to produce a measurable signal for detection. In this technology, the nanoscale procedures lead to handheld devices that are stable, highly sensitive, and marketable [44,45]. Finally, nanotechnology-based approaches can be a promising tool to enhance the potency and selectivity of physical, chemical, and biological therapies with minimized toxicity to normal cells. Targeted NPs have been designed to deliver lethal doses of therapeutics actively or passively to pathogenic cells [46]. This nanotechnology in COVID-19 mainly focuses on disrupting the cell receptor ACE2 interaction through different approaches, including recombinant ACE2, antibodies, and protease inhibitors to scavenge the virus, interfering with the spike/ACE2 interaction, and inhibit the spike protein processing, respectively [20].

2.1 Prevention

The SARS-CoV-2 virion is primarily transmitted by air spreading to the entire respiratory system of the human body. Afterwards, the virion is functionally larger due to the presence of other airway materials (i.e., bacterial cells and epithelial cells) in the liquid droplets of the respiratory tract. The large droplets (>150 µm) show a low evaporation rate, which affects the aerosolized virus survival, transport, and fate. This virion is stable at RT and 4°C but inactivated under ultraviolet (UV) light and extreme pH conditions (pH > 12 and pH < 3), and heating at 65°C for 5 min [20]. Considering transmission, COVID-19 spreading should be controlled personally and environmentally. According to Figure 2, maintaining vaccination, personal protective equipment (PPE), and environmental sanitation are practical ways that lead to widespread community-level protection [47]. This section outlines the potential applications of nanotechnology for reducing infection risks to people, with a specific focus on several individual and environmental factors. Recent studies using NPs for infection prevention are shown in Table 4.

Figure 2

Schematic illustration for infection prevention against COVID-19.

Table 4

A semi-exhaustive list of selected NPs for infection prevention against COVID-19

	Organic NPs				Inorganic NPs	Inorganic/organic NPs
	LNPs	Protein NPs	Polymer NPs	Carbon-based NPs	Inorganic NPs	Inorganic/organic NPs
Vaccination	mRNA of RBD/LNPs [52], Spike protein/LNPs [53]	Spike protein/ferritin [64], RBDs/ferritin [65,67], RBD/aldolases [62,63]	DNA/PLA [84]	Recombinant peptide-modified nanodiamonds [97]	Spike protein/silica NPs [93]	mRNA-1273/PEGylated lipids [86]
PPE	nano-micelles of Rha(s) [99]	—	Synthetic polymers/oligomers [100], licorice roots extract/PVA [101]	G [102], polydopamine/GO [103]	Zn [104], Cu [105], Ag NPs [106], MOFs/Cu/Zn [107], Ag nanocluster/silica composite [108]	TiO₂ nanotubes/CS/PVA, CS/PVA, and silk/PVA [109], shellac/CuNPs [110], PVDF/PS nanofibers/Ag/Zn coated cotton [111]
Water and wastewater Treatment	—	—	CS [112]	CNTs/GO/PP [113]	Cu/TiO₂ nanofibers [114]	TiO₂/G nanohybrid materials [115]
Air purification	—	—	PMMA/PDMS/CS [116]	Laser-induced G [117], MWCNTs/PF [118]	Ag NPs [119], AgNP/SiO₂ hybrid particles [120], Ag/Al₂O₃ and Cu/Al₂O₃ [121]	nano-Ag/TiO₂/CS [122], TiO₂/crystal violet nanocomposites [123], ZnO NPs/PVA/KGM [124], nano-Ag/TiO₂/CS [122]
Surface disinfection	—	—	CS [125]	—	TiO₂ [126], AgNPs [127], silica [128]	AgNPs/cellulose [129], Cu₂O/polyurethane [130]

2.1.1 Vaccines

Despite a lengthy and complicated vaccination procedure in resolving the pandemic outbreak, it is highly effective. An effective vaccine is composed of antigens, adjuvants, immune enhancers, and delivery systems, which activates the immune system by generating neutralizing antibodies and T cells [48]. Many trials have been done to develop an effective vaccine that targets full-length spike protein or RBDs [49]. Currently, conventional vaccine production platforms include inactivated virus, live-attenuated, subunit-based, viral vector-based, and DNA/mRNA vaccines [47,49]. Although inactivated and live-attenuated vaccines have a rapid manufacturing process, the live-attenuated vaccine is innately immunogenic by affecting the toll-like receptors and may recover virulence. Nonetheless, inactivated vaccines are more stable and safer than live-attenuated vaccines; the antigens may be destroyed during inactivation [43,47]. Beijing-based Sinovac Biotech (NCT04383574, NCT04352608) is one of the groups that developed the inactivated vaccines [20]. Subunit vaccines are recombinant spike proteins with low immunogenicity, immunological memory, and stability but high safety and low side effects [47,49]. Adjuvants might be added to increase immunogenicity and reduce the number of vaccine cargos per dose [49]. Novavax (NCT04368988) developed a subunit vaccine containing an adjuvant named saponin-based Matrix M [20].

Viral vector-, DNA-, and RNA-based vaccines are gene delivery systems to trigger a vigorous immune response. Due to their intrinsic adjuvant activity, non-replicable viral vectors have a strong immune-stimulating effect [49]. The University of Oxford/AstraZeneca is one of the groups that developed adenoviral vector vaccines to produce the SARS-CoV-2 spike protein [20]. Another member of the genetic vaccine is the DNA vaccine. However, the synthetic DNA vaccine is thermostable and shows lower titers of antibodies than other vaccination strategies, and viral genome integration into the host DNA may lead to cancer. A DNA plasmid vaccine developed by Inovio Pharmaceuticals (INO-4800) is currently undergoing human Phase I testing (NCT04336410) [20]. The RNA vaccine contains mRNAs or siRNAs that switch off crucial target genes or synthesize vital virus proteins [20]. However, effective RNA delivery to the target is challenging because of the thermosensitivity of RNA, insertional mutagenesis risk, and anti-vector immunity [47]; they can elicit high levels of neutralizing mAbs and memory B cells and broaden the response to different variants [21].

Nanomaterials have already played key roles in vaccine delivery systems due to their stability, immunity, and delivery [20]. The relatively safe NP-based vaccines present antigens in their original forms [50] and stimulate antigen-specific immune responses even without adjuvant [51]. These nanovaccines can intrinsically or extrinsically activate the immune system because of functionalization or antigenic cargos. Biocompatible lipid, protein, polymer, carbon-based, and inorganic NPs can encapsulate antigenic cargo with high loading efficiency and improve pharmacokinetics. Major NP platforms are lipid NPs (LNPs) and protein NPs. LNPs, containing ionizable lipids, demonstrate strong potential as a gene delivery system with high loading capacity, transfection efficiency, and endosomal escaping to stabilize and protect them from degradation [43]. In two studies, LNPs were utilized for mRNA delivery of RBD [52] and full-length spike protein [53]. The current US FDA-approved mRNA-based LNP vaccines are BNT162b2 and mRNA-1273, developed by Pfizer/BioNTech and Moderna, respectively [54,55,56]. To improve the real-world effectiveness of the vaccine, alphaviral replicase was added to the RNA sequences and replaced the mRNA’s untranslated region (UTR) with a synthetic UTR to self-amplify the RNA and increase protein translation, respectively [49]. There are also adjuvant-encapsulated LNPs such as QS-21 included in the liposomes decorated with RBDs [57] and alum-packed on the squalene [58], which effectively activates the humoral and cellular immune system.

Protein-based NPs are constructed through self-assembling monomers, which are subsequently covalently or noncovalently bound to viral antigens [43]. These antigen-presenting NPs imitate the viral structure and elicit potent immune responses, which are helpful in reducing the immunogenicity of protein-based vaccines [59]. Popular proteins for vaccines are ferritin [60,61] and aldolase [62,63]. Recently, full-length spike protein/ferritin [64], RBDs/ferritin [65], RBD-24-mer/ferritin [66], and RBD/aldolases [62,63] were generated as a possible vaccine against the virus. Ma et al. conjugated RBD and/or heptad repeat to the 24-mer ferritin to induce humoral and cellular immune responses [67]. Ferritin can self-assemble into octahedral particles with three-fold axes and present multiple ordered viral antigens on the particle surface [68]. Scientists have also designed nanomer peptide vaccines using a new strategy, immunoinformatics, to map and identify epitopes in the SARS-CoV-2 protein sequences [69]. Sahoo et al. predicted SARS-CoV-2 nanomer epitopes for T-cell against class I and II of major histocompatibility complex, which may serve as sensitive, rapid, and cost effective vaccines [70]. Protein-based NPs can also be created with manufactured nanocomponents with adjuvant characteristics to induce immune responses [20].

Natural and synthetic polymers (Figure 3) have also been explored to prepare nanovaccines due to higher immunogenicity, biodegradability, biocompatibility, and a large surface area for targeting [71]. They are specifically developed in local and topical medications by considering their positive zeta potential to show higher immune stimulations and lower poly(ethylene glycol) (PEG) concentration to decrease the barriers [49]. These polymeric NPs, as carriers or adjuvants, can induce remarkable anti-inflammatory, antibody, and T-cell cross-reactivity responses. Chitosan (CS) [72,73], trimethyl CS/hyaluronic acid [74], β-cyclodextrin/CS [75], alginate/CS [76], dextran [77], pullulan [78], and inulin [79] are examples of natural polymers utilized in vaccine delivery systems. Chitosan NPs (CSNPs) have been extensively studied in vaccine area owing to their biodegradability, biocompatibility, lack of toxicity, and ease of shape and size processing [80]. Tailor-made polymers also offer certain advantages such as reproducibility in chemical, biological, mechanical, and interfacial properties [71]. They are mainly poly(lactic-co-glycolic) (PLGA) [81], poly(ϵ-caprolactone) [82], dendrimers [83], poly(lactic acid) (PLA) [84], polyanhydride [85], and PEG [86]. Among these synthetic polymers, PLGA and PLA consider major synthetic polymers for mucosal antigen delivery [87]. Biopolymers as adjuvants can be conjugated with various antigens for intranasal delivery and trigger a strong immune response, but the proper type of polymer and the antigen affect the vaccination success [20,71].

Figure 3

Few examples of natural and synthetic polymers.

Inorganic NPs are usually derived from non-natural materials. These intrinsically immunogenic materials show unique optical, electric, and magnetic properties making them promising vaccine design options [88]. The key categories of the inorganic NPs’ library are AuNPs [89], quantum dots [90], carbon nanotubes (CNTs) [91,92], silica NPs [93], iron oxide NPs [94], graphene (G) [95,96], and nanodiamonds [97]. It is important to note that the functionalization of these inorganic NPs with a vast number of molecules, or specific motifs, is typically required for intrinsic (i.e., solubility and biocompatibility) and extrinsic (i.e., vaccine efficiency) capacities of the vaccines and improves human defense against random viral mutations and antigen shape changes [20,98]. Orecchioni et al. functionalized graphene oxide (GO) with amino groups to induce stronger cellular immunity with negligible toxicity [95]. Xu et al. also engineered GO–PEG–poly(ethyleneimine) (PEI) as a vaccine adjuvant for a robust stimulation of the immune system [96].

2.1.2 PPE

Proper PPEs (i.e., masks, hand sanitizers, etc.) are critical for contagious respiratory illnesses such as influenza and COVID-19, which spread through aerosol particles or droplets. According to Asadi et al., these aerosols can transmit using two possible modes: (1) droplet sprays (>5 µm) during a sneeze or a cough, which usually collect in the upper respiratory tract, and (2) inhalation of microscopic aerosol particles (<5 µm), which reaches in the deep lungs, enters the host cell and impairs multiple cellular functions [131]. Therefore, developing PPEs would significantly prevent the risk of infectious disease transmission by immobilizing the aerosols and eradicating the virus [47].

A conventional PPE mask serves as a physical barrier whose filtration efficiency only depends on the particle size and the airflow rate. They have neither been functionalized with biocides nor filtered out particles with sizes ∼0.3 µm in the high airflow rate. Therefore, the newly designed masks should be dual-functional, which can increase the effectiveness of the existing masks by reducing the pore sizes under 100 nm and inducing the virucidal activity on the spot. For example, antiviral N95 masks, the most common respirators, arrest different particles through four mechanisms such as impaction (>500 nm), interception (>200 nm), diffusion (<200 nm), and electrostatic attraction, in which larger particles become surface blocking, smaller particles pass through the fibrous matrix deeply, and oppositely charged particles attract electrostatically [132]. The humid-exhaled air leads to swelling hygroscopic droplet nuclei, which influence the filter’s ability to trap particles. Moreover, nanotechnology aims to synthesize superfine filters with high efficiency in improving particle capture and retention characteristics, reducing the impacts of exhaled humid air on particle redistribution, and quickly inactivating viruses upon capture [20].

There are several non-electrospinning and electrospinning techniques for nanofiber fabrication. The effectiveness of electrospinning for nanofiber production led to widespread usage in polymer nanofiber production. Over the last two decades, traditional electrospinning has developed into other derivative methods such as multi-jet electrospinning, needleless electrospinning, and bubble electrospinning [133]. These electrospun nanofibers only arrest the smallest virus-laden droplets and stop their transmission in the mask [20]. Nonetheless, nanofibers decorated with antiviral compounds such as G nanosheets, metal/metal oxide NPs, and polymer NPs can deactivate the pathogens, too. G-coated masks exhibited potent antiviral activity due to negatively charged particular nanosheet components [102]. Polypropylene (PP) filter surface spray-coated by GO and polydopamine [103], cotton/silk fabrics containing Ag/Cu NPs, and rGO [134] are examples of multifunctional electrospun nanofibers, which show an antiviral activity against pandemic SARS-CoV-2. Jeong et al. recently suggested a one-step nanocoating method to fabricate commercial facial masks. They synthesized a photo biocidal-triboelectric nanolayer composed of crystal violet as a photosensitizer, silica–alumina for photosensitizer immobilization, and perfluorooctyltriethoxysilane to improve wetness resistance and triboelectric effect [135].

Metal ions are characterized by oligodynamic effects to inactivate virions. Zn ions embedded polyamide 6.6 fibers [104], Cu-coated PP mask [105], CuO-impregnated masks [136], Ag NPs [106], and photocatalyst ZnO nanorods and Ag NPs loaded on poly(methyl methacrylate) [137] are the examples with antiviral activity of metal/metal oxide. FFP3 protective masks coated by Ag nanocluster/silica composite also demonstrated the virucidal effect [108]. TiO₂-coated nanofibers control and mitigate submicrometer airborne virus particles upon solar and UV radiation. These nanofibers demonstrated superior photocatalytic, photoinduced hydrophilicity, and antibacterial activity [138]. Metal–organic frameworks (MOFs) coated onto PP were also utilized as filter mask materials. Controlled release of Cu and Zn ions from ZIF-8 encapsulated Cu nanowires has proved antiviral efficiency [107].

Abbas et al. have also declared the antiviral activity of polymeric mixtures incorporated with inorganic compounds. They fabricated three-layered electrospun nanofiber masks composed of TiO₂ nanotubes/CS/poly(vinyl alcohol) (PVA), CS/PVA, and silk/PVA. The outmost layer of TiO₂/CS/PVA displayed antibacterial activity via the double effect of TiO₂ (oligodynamic effect) and CS (acidic hydrophilic environment) [109]. Kumar et al. also reported a photoactive antiviral nanocomposite containing CuNPs, shellac, and a hydrophobic natural biopolymer, which conferred reusable self-cleaning surgical masks [110]. In another study, a disinfecting reusable facial mask was constructed by combining nanofibers of electrospun poly(vinylidene fluoride)/polystyrene (PS) with Ag/Zn-coated cotton [111]. The effectiveness of face masks can also be increased by combining polymers and other organic materials. For instance, synthetic polymers conjugated with oligomers developed antimicrobial activity under UV and visible light irradiation [100]. Other study utilized an electrospinning mixture of PVA and licorice roots extract containing glycyrrhizin acid and glycyrrhizin to synthesize a membrane for viral inactivation [101].

Hand sanitizer should be immediately performed before putting on and after taking off all PPE. They are utilized with soap hand washing to inactivate the virus and prevent its transmission. Few nano-based hand sanitizers mitigate transmission and control infection levels [139]. Biosurfactant with antimicrobial activities, and low dermal and irritation toxicity attracted much attention as an active ingredient for hand sanitizers [140]. Bakkar et al. synthesized nano-micelles of rhamnolipids (Rha(s)) as a potent bactericidal agent against both Gram negatives and positives. They proposed that hand sanitizers containing these nano-micelles’ critical concentrations might be utilized against SARS-CoV-2 [99]. AgNPs represent a promising hand sanitizer ingredient if the toxicity on the skin and the environment is considered. Therefore, Fibriana et al. biosynthesized AgNPs from liverwort and demonstrated their antimicrobial activity in a non-alcoholic gel form hand sanitizer [141]. Although they did not evaluate the antiviral activity of the sanitizer, the virucidal activity of AgNPs has been confirmed against SARS-CoV-2 in another study [127]. Other effective disinfectants, formulated into nanocomposites and replaced with alcohol-based hand sanitizers, are herbal plant roots with low toxicity [142].

2.1.3 Water and wastewater treatment

Stools and masks are considered the main reason for polluting water and wastewater with coronavirus [143]. Enveloped viruses, including influenza viruses and coronaviruses, are too sensitive to the water environment and are often inactivated rapidly [144]. Nonetheless, shelf-life in water circumstances relies on characteristics such as pH, temperature, the concentration of suspended solids, and organic materials [143]. Rimoldi et al. declared that although SARS-CoV-2 RNA was present in water and raw wastewater, virus infectivity was negative [145]. In any way, the most reliable way to prevent virus transmission is the disinfection of water and wastewater. The water disinfection process includes a broad spectrum of treatment methods ranging from conventional treatment techniques (i.e., chlorine in swimming pools, ultrafiltration, nanofiltration, and reverse osmosis membranes) to advanced membranes (i.e., nanocomposite, distillation, bioreactor, and photocatalytic reactor) [143,144]. Herein, we focus on the most commonly used membranes based on nanotechnology with high permeability, selectivity, and antiviral activity.

Nanocomposite membranes remove charged contaminants such as bacteria and viruses from a watery component. Electrostatic interaction between the reactive functional groups of the membrane components and charged contaminants make them efficient [146]. Metal/metal oxide particles are the most used reactive compounds, affecting the membrane’s permeability through hydrophilicity characteristics and antimicrobial properties due to their positive surface charge and nano-sized properties [146]. Antiviral biopolymer and its natural cross-linker were utilized in reversible coronaviral particles’ adsorption in another study. Ciejka et al. developed novel nano/microspheres obtained by crosslinking CS with genipin, which could strongly adsorb HCoV-NL63 virus [112]. They suggested that the obtained material may be applied to purify water from pathogenic coronaviruses [112].

Membrane distillation is a thermal process that utilizes water vapor through a hydrophobic porous membrane under differential temperature, and occasionally nanotechnology for thermophilic pathogens’ disinfection [147]. The primary pathogen disinfection mechanism is embedding biocidal NPs such as CNTs into the hydrophobic membrane [113] or coating the membrane with a polymer containing biocidal NPs [148]. Gupta et al. also reported on the biocidal activity of CNTs and GO coated onto a PP membrane, attributed to oxidation stress of GO, and diameter-dependent piercing and length-dependent wrapping of CNTs [113]. Because of the immediate inactivation of SARS-CoV-2 at high temperatures [149], this dual barrier strategy, temperature/vapor pressure, is an exemplary process for virus removal.

A photocatalytic membrane reactor is a combination of photocatalysis and membrane separation for effective water purification. In photocatalysis reactions, semiconductor bombardment with low energy plays a crucial role in delivering excited electrons and holes for subsequent redox reactions [146]. There are different light-responsive transition metal oxides with the potential to deactivate harmful viruses [150]. TiO₂, the most effective photocatalyst, produces a significant amount of reactive oxygen species (ROS) after exposure to UV-A light to inactivate microorganisms like bacteria and viruses [151]. Zheng et al. showed that the Cu-TiO₂ nanofibers had a brilliant capacity to remove bacteriophage f2 and Escherichia coli under visible light [114]. To achieve water treatment in the presence of TiO₂, mass transfer rates should be minimized because photocatalysis happens, especially on the TiO₂ surface [115]. The other photocatalysts that attracted much attention are carbon-based materials because of no metal ion leaching in the water environment and optimal natural light-harvesting capacity [152]. These carbon-based materials such as fullerene [153], CNT [154], carbon dot (CD) [155], and graphitic carbon nitride [156] have been utilized for the inactivation of viruses. Due to the polymer membrane damage after prolonged exposure to light, ROS production, and photocatalyst agglomeration [157], developing a flexible high-performance photocatalytic membrane is an urgent challenge for water/wastewater purification.

2.1.4 Air purification

Evidence proves that the COVID-19 virus can be transmitted through air and survive in tiny aerosol droplets for a few hours [158]. Conventional disinfection strategies for removing bioaerosols are non-thermal plasma, photocatalytic oxidation (i.e., UV, ozone, hydrogen peroxide), and air filters with photocatalytic activity. Electrospray ionization of active ingredient solutions, engineered water nanostructures (EWNS), is another way of inactivating airborne microorganisms through ROS production [159]. Each of these innovations could be useful in environmental chambers, but few are able to effectively combat the ongoing environmental and pathogenic disturbances in a real-world situation. Ideal air disinfection should result in effective reduction of key air pollutants, pathogens, disease transmissions, and finally, real-world clinical infections [160]. Filter media have the most significant practical potential of all strategies. They consist of myriad interwoven nanofibers utilized in mechanical ventilation systems to decrease airborne infectious disease transmission [161]. Nonetheless, these bioaerosols can multiply on these filters due to high moisture [119].

A wide range of materials, including metal/metal oxides, carbon-based nanomaterials, and biopolymers, play an important role in manufacturing efficient antiviral filters [132]. The Ag aerosol NPs generated from atomizers are efficient antimicrobial sanitizers to improve air quality passing through air filters [162]. AgNPs can improve the air quality alone or in incorporation with other supportive materials [119]. Young et al. utilized hybrid NPs of Ag-SiO₂ on air filtration units with a synergistic bactericidal effect on Gram negatives and positives [120]. Ag/Al₂O₃ and Cu/Al₂O₃ as supportive catalysts are useful in air-cleaning technologies because they can inactivate the SARS-CoV virus in a few minutes [121]. A multifunctional air filter composed of AgNPs-paper towel microfibers and aligned zein nanofibers also exhibited an effective antimicrobial activity [163]. The use of TiO₂ photocatalysis would also be helpful for air disinfection in ventilation and air filtration systems [20]. The other functionalized filter exhibited a potent inactivation of various bioaerosols under visible light in the presence of TiO₂–crystal violet nanocomposites. In this combination, crystal violet induces ROS production directly by itself or indirectly with the help of TiO₂ [123]. ZnO NPs were also utilized to induce photocatalytic and antibacterial activity to PVA and konjac glucomannan (KGM)-based nanofiber membranes [124].

Due to their unique physicochemical characteristics, such as high specific surface area, electrical conductivity, chemical/mechanical stability, and customizable structural properties, carbon-based nanomaterials also have antiviral activity [164]. Stanford et al. demonstrated a self-cleaning air filter made of laser-induced G to eliminate bacteria that can lead to illness and unfavorable biological reactions [117]. In comparison to cellulose fibers, the filter papers made of multi-walled carbon nanotubes (MWCNTs) and phenol-formaldehyde (PF) demonstrated a high specific surface area and efficient particle interception [118]. Among biopolymers, CS showed great capacity in air filter media construction. An electrospun superhydrophobic/superhydrophilic fibers composed of poly(methylmethacrylate)/polydimethylsiloxane and CS demonstrated a high bactericidal effect on E. coli and Staphylococcus aureus [116]. Wang et al. also showed the effective removal of viral aerosols (airborne MS2 bacteriophage) through nano-Ag/TiO₂-CS filters [122].

2.1.5 Surface disinfection

The WHO advises thoroughly sanitizing any contaminated surfaces with water, detergent, and disinfectants even if it has not been confirmed that certain surfaces can transmit CoVs to hands [37]. There are biological (i.e., probiotics or biosurfactants), chemical (i.e., hydrogen peroxide or metal ions), and physical (i.e., UV radiation) strategies frequently used in traditional disinfection techniques. Nanotechnology offers pathways to inactivate surface-bound and airborne viruses through spray NPs on the surfaces or develop innovative self-disinfecting surface and surface coatings [20]. These NPs are metal/metal oxide, G nanosheets, and biopolymer NPs, which can also be functionalized with antibodies against virions to improve antiviral potency [49].

Electrospray EWNS-based nano-sanitizers [159] and AgNP-loaded cellulose-based wipes [129] indicated an efficient reduction in influenza H1N1/PR/8 and MERS-CoV concentration on surfaces, respectively. The promising approach for inactivating surface-bound viruses is photodynamics, which attacks target cells via photosensitive agents’ excitation and leads to cell death by producing ROS. Zn phthalocyanine grafted onto upconverted sodium yttrium fluoride NPs coated by PEI was used by Lim et al. to provide a potential method for the viral photodynamic inactivation [165]. TiO₂ photocatalysis would also be very helpful for surface disinfecting through TiO₂-doped paints after being exposed to UV light [166]. According to Khaiboullina et al., UV exposure for 1 min completely eliminated coronaviruses on a TiO₂ NP-coated surface, aiding in the creation of self-disinfecting surfaces in public and healthcare facilities [126]. The glass or stainless steel coated by Cu₂O particles bound with polyurethane showed antiviral activity [130]. In contrast to stainless steel, Cu brasses or alloys containing Cu would offer efficient antibacterial surfaces for healthcare facilities [158]. CuNPs can eliminate viruses when sprayed on infected surfaces [136], but it is important to look into their antiviral effectiveness against SARS-CoV-2. AgNPs can also be modified to interact more effectively with viral proteins through surface capping agents. Through such tuning, the binding preference for viruses may be improved while the host cells’ toxicity is decreased [127]. Iron oxide NPs can also be utilized for sanitizing surfaces due to lipid peroxidation, ROS production, and neutralizing surface proteins of viruses [167]. The surface plasmon resonance of the AuNPs demonstrated that these antiviral agents have mechanisms comparable to Ag and Cu [168].

In addition, fullerene and G are promising candidates for photodynamic virus inactivation and have demonstrated efficacy against a variety of viruses such as the IAV [169]. Due to the cytotoxicity of metal NPs, nanomaterials of natural herbs such as the positively charged CDs obtained from curcumin have been investigated and showed an inhibitory effect against a coronavirus model [170]. Another promising non-toxic NPs are CS-based NPs with potential antiviral activity against coronavirus. Milewska et al. reported the antiviral action of N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) against coronavirus HCoV-NL63 entrance [171]. Milewska et al. also confirmed HTCC’s inhibitory effectiveness on SARS-CoV-2 and MERS-CoV coronavirus [125]. Poly(diallyldimethylammonium chloride) and poly(acrylic acid) polyelectrolyte multilayers are also utilized as antimicrobial nanocoating solutions [172]. Through an electrostatic attraction between the coronavirus’s anionic spike protein and the cationic surface of these charged NPs, the microorganisms are rendered inactive [172]. In addition to the attractive effect of charged nanomaterials, the repulsive force of superhydrophobic silica nano-surfaces can also prevent the SARS-CoV-2 adhesion on surfaces [128].

2.2 Diagnosis

However, reverse transcription polymerase chain reaction (RT-PCR) is predominantly utilized in the accepted traditional method for detecting SARS-CoV-2 [20]; nanotechnology is of great interest and comparable with RT-PCR owing to specific and rapid detection of infections (e.g., viral proteins and RNA) and immunities (e.g., IgM/IgG) [49,173]. These NPs show two unique properties: (1) interacting with specific biomarkers and (2) transferring interacting events into measurable signals. The first step performs through surface functionalization of NPs and the second one requires unique physicochemical properties of NPs including optical, reactivity, or fluorescent properties [49,174]. Table 5 demonstrates diagnostic platforms in NPs for quick and precise SARS-CoV-2 detection.

Table 5

Various SARS-CoV-2 diagnostic platforms in NPs for quick and precise detection

Technique	NPs	Components
LFIA	Inorganic NPs	Polyclonal antibodies/AuNPs [173], anti-human IgM/AuNPs [175], spike protein/AuNPs [176], glycan/AuNPs [177], nucleocapsid protein/AuNPs [178], spike protein/SiO₂ core/Ag shell/dual layers of Raman molecule [179]
	Inorganic/organic NPs	Anti-human IgG/lanthanide-doped PS NPs [180]
	Others	Nucleoprotein/selenium NPs [181], S9.6 antibodies/fluorescent NPs composed of carboxylated europium chelate [182]
Electrochemical biosensor	Carbon-based NPs	Anti-spike protein antibody/G [183]
ELISA	Polymer NPs	Anti-spike protein antibody/TMB/PLGA [184]

One colorimetric detection technique is lateral flow immunoassay (LFIA) based on nanomaterials with optical properties. To detect viral proteins, most platforms are built on AuNPs and functionalized using polyclonal antibodies [173]. Anti-human IgM-functionalized AuNPs were created by Huang et al. to identify SARS-CoV-2 nucleoproteins colorimetrically [175]. In a different study, spike proteins were conjugated with AuNPs to detect virus-specific antibodies (IgM/IgG) [176]. Baker et al. utilized the immobilized glycan-AuNPs to diagnose glycan and spike protein interactions [177]. Through the use of complementary DNA sequences of the nucleocapsid protein, AuNPs can also target SARS-CoV-2 RNA [178]. Another nanomaterial introduced into LFIA constructure is SeNPs, with low toxicity and high biocompatibility. They were functionalized with the SARS-CoV-2 nucleoprotein to enable the colorimetric detection of virus-specific antibodies [181]. Comparable to commercial AuNP-based LFIA, the SeNP-based LFIA displayed higher and similar sensitivity to virus-specific antibodies, IgM/IgG, respectively [49].

Fluorescent NPs conjugated with S9.6 antibodies are also nanomaterials to capture specifically the hybridized viral RNA–DNA probe on a strip. The SARS-CoV-2 genome including nucleocapsid, conserved ORF1ab and envelope proteins are targets for DNA probes [182]. In a different approach, anti-human IgG was coupled to lanthanide-doped polysterene NPs to generate a highly sensitive fluorescent signal for the detection of SARS-CoV-2-specific IgG [180]. A surface-enhanced Raman scattering (SERS)-based LFIA was reported by Liu et al., which detects simultaneous anti-SARS-CoV-2 IgM/IgG with high sensitivity. They synthesized SiO₂ NPs composed of three parts: SiO₂ core, Ag shell, dual layers of Raman molecule, and spike protein with a specific target for IgM/IgG. They confirmed that SERS-LFIA demonstrated a significantly higher detection limit than commercial Au NP-based LFIA [179]. There are also peptide aptamers, Affimers, that might replace antibodies in LFIA structure. Affimers are non-antibody scaffolds that bind to target molecules. LFIA based on proprietary Biotinylated anti-SARS-CoV-2 S1 Affimer® is an ultra-sensitive technique produced against S proteins of the SARS-COV-2 [185]. They demonstrate advantages over conventional antibodies, including smaller size, more versatile, remarkable stability against pH and temperature, and equivalent affinity with higher specificity [186].

G was utilized to construct a field-effect transistor-based biosensor because of superior electrical and optical capabilities. The performance of the G-based biosensor coupled to a specific anti-spike protein antibody was determined in samples from nasopharyngeal swabs and cultivated viruses [183]. The use of G derivatives in electrochemical biosensors has attracted much attention. Singh et al. engineered a microfluidic chip with rGO linked to specific antibodies of the influenza virus, H1N1. This microfluidic immunosensor could capture several viral species and provide a promising platform for effective detection [187]. Khoris et al. conjugated anti-spike protein antibody with tetramethylbenzidine (TMB)–PLGA NPs in an improved ELISA method. The absorbance of the oxidized TMB in the presence of nanomaterial with peroxidase-like activity shows spike protein concentration [184].

2.3 Treatment

In the COVID-19 pandemic, different research activities experienced a considerable uptick in getting efficient and secure therapies. COVID-19 therapy is done initially by lopinavir (HIV medication) and remdesivir (Ebola medication) for hospitalized patients who need extra oxygen, favipiravir (influenza medication) in the clinical status of patients, and corticosteroids such as dexamethasone for critically ill patients [188]. The primary drawbacks of existing treatments are the absence of broad-spectrum antiviral drugs, the free drug molecule restrictions, and the biological barrier [20]. Therefore, there is an increased interest in developing innovative, broad-spectrum antivirals, which can combat various mutations of the spike protein and be less likely to develop resistance. The NPs are one of the most efficient ways to enhance the solubility of weakly soluble pharmaceuticals, lengthen the half-life of circulation, and achieve controlled/targeted drug release.

Because the lungs are the most critically affected organ, the medicine should target the essential host cells in the deep lung. Therefore, aerosol-based nanomaterials can be an effective carrier to penetrate the deep airways and deliver the therapeutics to the virus reservoir (i.e., alveolar type II cells) and block the binding of ACE2 receptors with spike protein [20]. Intravenous injection is the other route of administration, where antiviral medication NPs most likely optimize exposure. The challenge of non-specific interactions in systemic drug delivery might be overcome by the negative surface charge of NPs [49]. These NPs can be designed to halt viruses as therapeutics or act as a delivery vehicle for antiviral drugs. Therefore, this study focuses on NPs as intrinsic antiviral agents and therapeutic carriers (Table 6).

Table 6

A semi-exhaustive list of selected NPs as intrinsic antiviral agents or antiviral drug carriers

	Organic NPs			Inorganic NPs
	LNPs	Polymer NPs	Carbon-based NPs
NPs as intrinsic antiviral agents	—	Alginate [189], sulfated glycomimetic oligomers and polymers [190], NPs decorated by HSPG or SA mimics [20], glycosylated dendritic polymers with 3′-sialyllactose- and 6′-sialyllactose [191]	G [192], multivalent disaccharide/[60] fullerene nanoballs [193]. Glycyrrhizic acid/CDs [194]	Ag NPs [127], bimetallic Fe/Cu NPs [195]
NPs as antiviral drug carriers	mRNA/β-sitosterol-doped LNPs [196], membrane NPs [197]	IVM/PLGA-b-PEG-Mal [198], membrane NPs of PLGA [199]	—	Chloroquine and hydroxychloroquine/Ag, Au, Ag/Au, and Pt NPs [200], polyphosphate/silica NPs [201]

2.3.1 NPs as intrinsic antiviral agents

Several recent studies have described the inherent antiviral activity of NPs, including metal/metal oxides, carbon-based nanomaterials, and biopolymers, which disrupt the viral integrity, produce ROS, or generate heat to kill the viruses [49]. Inorganic NPs such as Ag [202,203,204], Cu [205], Au [206], and Ti [207] show intrinsic antiviral activity, which is size and dose dependent. Ag NPs’ antiviral effects are mediated by various mechanisms, including the generation of ROS leading to membrane/envelope damage and toxic Ag(i) forms with a strong affinity for the thiol groups of structural and functional proteins [127]. The antiviral activity of Cu and CuO NPs is related to Cu ions’ attacks on viral proteins and lipids and ROS production, too. Because of oxidation–reduction reactions, the viral disinfectant properties of CuNPs can be further enhanced when combined with bimetallic particles such as Fe [195]. NPs and nanorods of Au inactivate viruses in plasmonic photothermal treatment through intense heat emission and altering the membrane and/or surface functional groups [208], while believed to be far less harmful than Ag NPs [20]. TiO₂ inactivates SARS-CoV-2 through their photocatalytic properties under UV light by ROS production, which damages cell walls, membranes, DNA, and proteins [207]. However, viruses that are enveloped may be more protected than those that are not [209].

Carbon-based nanomaterials, such as G [192], fullerene [193], and CDs [194] are under investigation in COVID-19 treatment owing to antimicrobial activity through membrane distortion, biocompatibility, biodegradability, and tissue regeneration induction [210]. Sharp edges and negatively charged surfaces of G derivatives lead to electrostatic interaction with the positively charged virus particles [211,212]. Gholami et al. generated G-based heparin biomimetics through sulfating functionalized rGO sheets with biocompatible hyperbranched polyglycerol, which demonstrated antiviral activity on orthopoxvirus and herpesvirus strains [213]. Javier et al. also demonstrated in vitro antiviral activity of a multivalent disaccharide/[60] fullerene nanoballs against the Dengue and Zika viruses [193]. Finally, CD derivatives modified by an active compound (glycyrrhizic acid) demonstrated antiviral effect on porcine reproductive and respiratory syndrome virus through inhibition of proliferation, stimulation of innate immune responses, and inhibition of ROS accumulation [194].

Various polymeric compounds have antiviral activity, which comprises polymer length, hydrophilicity, and charge [20]. In nucleic acid polymers, phosphorothioated oligonucleotides were utilized to inhibit the entrance of hepatitis B and hepatitis D viruses and HBsAg release against hepatitis B virus [214]. In polysaccharides, negatively charged polymers are perhaps the most widely studied, which show a broad-spectrum antiviral effect on a variety of viruses. Alginate is an example of a negatively charged polysaccharide that shows antiviral activity due to the charge and phenolic structure [189]. Sulfated compounds with antiviral properties, including sulfated glyco-oligomers and glyco-polymers [190], Fucoidan-mimetic sulfated glycopolymers [215], PS sulfonate, PVA sulfate, polymethylene hydroquinone sulfonate, naphthalene sulfonate [214], dextran sulfate [216], heparan sulfate [190,217,218], dendritic polyglycerol sulfate [219], and carrageenan [190,220,221,222] are attributed to length and sulfate content. For instance, heparin sulfate blocks the non-specific cell surface adsorption by preventing membrane fusion and interaction with viral glycoproteins [190]. Moreover, NPs decorated by heparan sulfate proteoglycan (HSPG) or sialic acid (SA) mimics demonstrated in vitro capacity to target most known respiratory viruses through binding to the attachment ligand of viruses and block their interaction with cell membranes [20]. Polymers modified by SA derivatives also exhibited antiviral activity due to the binding of virus HA to terminal sialic acid residues on cellular glycoproteins and glycolipids. So, Günther et al. worked on glycosylated dendritic polymers with 3′-sialyllactose and 6′-sialyllactose and confirmed that higher valency and spacing between ligands resulted in higher antiviral activity [191].

Positively charged polymers such as CS and its derivatives can also activate innate immune responses by upregulation of cytokines and chemokines, essential for preventing viral replication. Indeed, Zheng et al. demonstrated that pulmonary delivery of CS could induce widespread immune responses against the H7N9 influenza virus by increasing the number of macrophages, dendritic cells, and innate lymphoid cells [223]. PEG exhibits more near-neutral ζ-potential, and mPEG is synthesized by the replacement of the CH₃ moiety to the OH group of PEG. According to Kyluik et al., PEGylation of viruses with short-chain polymers can prevent infecting and invading viruses. In contrast, large chain polymers provide superior protection when grafted to host cells [224]. To permanently deactivate SARS-CoV-2, Cai et al. also reported a photothermal core–shell NP made of a semiconducting polymer and PEG functionalized with neutralizing antibodies [225]. The promising activity of the PEG polymer toward viruses is due to its water solubility [226], and high PEGylation of NPs may cause extended systemic circulation half-life [49]. Moreover, NPs made of antiviral polymers can affect viral infectivity by eradicating the virus effectively [20].

2.3.2 NPs as antiviral drug carriers

NPs are attractive controlled-release systems to deliver single conventional therapeutics (i.e., hydrophobic/hydrophilic small molecules and macromolecules) or synergistic delivery of multiple therapeutics to the target. Apart from lowering systemic toxicity and immunogenicity in normal tissues, NPs can offer unique characteristics to the therapeutics, including solubilization, bioavailability improvement, release prolongation, protection against harsh environments, and targeting passively and/or actively [227]. Effectiveness of passive and active targeting is influenced by the physical characteristics of NPs, including charge, hydrophilicity, size, functional groups, and the conjugated moiety on the surface [228]. Targeted NPs lead to higher cellular uptake in target cells and then drug release at the site of action [227]. Several NPs were proposed as promising drug delivery systems categorized as inorganic and organic NPs. The inorganic NPs with antiviral properties are promising drug delivery systems to the target site. Chloroquine and hydroxychloroquine were loaded onto metal NPs by Morad et al., who concluded that these nanostructures would be an appropriate candidate for COVID-19 treatment [200]. Silica NPs are the other inorganic NPs utilized for the delivery of polyphosphate. Polyphosphate was released gradually at the site, bound to the viral RBD electrostatically, and prevented further interaction between spike protein and host receptor [201].

LNPs, as organic NPs, can encapsulate macromolecules like mRNAs for SARS-CoV-2 suppression. For rapid ACE2 expression, which can compete with endogenous ACE2 in virus suppression, mRNA was encapsulated in β-sitosterol-doped LNPs. The mRNA can overcome limited half-life of recombinant ACE2 [196]. The antiviral potency of polymeric NPs can be enhanced by targeting and prolonging the controlled release of drugs. Targeted PLGA-b-PEG-maleimide (Mal) by an Fc immunoglobulin fragment was one of the polymeric NPs utilized to deliver hydrophobic ivermectin (IVM) and accumulate at the lung epithelia [198]. Nie et al. also noted that IAV virions bind significantly better to spiky NPs with 5–10 nm tall spikes. They predicted that cellular membrane coating and topography that matches geometry might develop nano-inhibitors for SARS-CoV-2 [229]. The other strategy for viral targeting and neutralization is coating polymer NPs with the cell membrane [199] or genetically engineered cell membranes [197,230] to mimic host cells through the critical surface receptors for viral binding. Zhang et al. synthesized PLGA NPs covered by either cell membrane of epitheliums or macrophages. These NPs are agnostic to current and upcoming coronaviruses since they are immune to various virus species and mutations [199]. In a different work, the genetically modified membranes were created by transiently transfecting human embryonic kidney (HEK)-293 T-hACE2 cells, after which cell membrane-based NPs were created via sonication and extrusion [197]. Rao et al. also made nano-decoys by fusing the cellular membrane of macrophages and HEK-293 T cells with a high level of hACE2. Moreover, many cytokine receptors were present on the fabricated NPs, which can efficiently bind and neutralize inflammatory cytokines like interleukin 6 and granulocyte macrophage colony-stimulating factor, as well as considerably reduce immunological dysfunction and lung damage in a mouse model of acute pneumonia [230].

3 Challenges and future perspectives of nanotechnology

Viral pandemics have introduced a global challenge to the scientific community in the past two centuries. However, many scientists believe that nanotechnology has the potential to overcome these pandemics; there are still several important challenges in high energy consumption, environmental safety, and human health that should be improved. Nanomaterial fabrication requires a lot of water and energy, and the chemicals used are often highly toxic to the environment and human health. Different factors, including the presence, concentration, and pH of organic or inorganic materials, which led to the long-term persistence of NPs in the environment, are well known as environmental pollutants [231]. Some physiochemical properties of the NPs cannot be protected by the immune and inflammatory systems and lead to immunotoxicity, inflammation, and oxidative stress, followed by severe cellular genotoxicity and fibrosis [45]. Therefore, the primary task is promoting the concept of safety by design and then performing the biocompatibility and biodegradability approaches using preclinical (in vitro and in vivo) and clinical studies for a candidate therapeutic, vaccine, medical device, or diagnostic assay [232]. Moreover, these viral pandemics require collective thought beyond ethnic frontiers and cultural diversity. To overcome such complicated challenges and achieve new and critical scientific solutions, a close collaboration among diverse researchers around the world with complementary skills is required [20]. According to this perspective, nanotechnology is an emerging technology where scientists from incredibly various backgrounds have collaborated successfully for improving complex issues in the diagnosis, detection, and treatment of viral diseases [233]. The “One Health” concept should be addressed in the future due to the interconnected health of humans, animals, and the environment.

4 Conclusions

Retroviruses have shown the potential for pandemic spread worldwide by their high contagious infections, which may lead to unexpected and very serious consequences. Although the current SARS-CoV-2 pandemic highly concerns, it is not among the most extreme threats encountered by humanity because science, technology, and innovation have enabled us to identify, control, and mitigate it. In fact, community hygiene and sanitation practices, effective vaccination, and treatment can shorten the duration of a pandemic. This work discussed nanotechnology’s potential as a platform for preventing, diagnosing, and treating COVID-19 and any future pandemics. There are different types of NPs proposed as promising foundations for counteracting the current global public health threat. These nanosystems are categorized into inorganic NPs (metal/metal oxides, silica) and organic NPs (lipid, protein, polymer, and carbon based) can be intrinsically or extrinsically immunogenic. Finally, the idea of “nanotechnology” can assist scientists in designing NPs for immune regulation in vaccine development and therapy, in the creation of quick, easy, and affordable assays for the diagnosis of COVID-19 and environmental sanitization.

Funding information: This work was supported by the Ministry of Education, Youth and Sports of the Czech Republic – DKRVO (RP/CPS/2022/005).
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Conflict of interest: The authors state no conflict of interest.

References

[1] Piret J, Boivin G. Pandemics throughout history. Front Microbiol. 2021;11:3594.10.3389/fmicb.2020.631736Search in Google Scholar PubMed PubMed Central

[2] Luby SP. The pandemic potential of Nipah virus. Antivir Res. 2013;100(1):38–43.10.1016/j.antiviral.2013.07.011Search in Google Scholar PubMed

[3] Doms RW, Moore JP. HIV-1 membrane fusion: Targets of opportunity. J Cell Biol. 2000;151(2):F9–F14.10.1083/jcb.151.2.F9Search in Google Scholar PubMed PubMed Central

[4] Illanes-Álvarez F, Márquez-Ruiz D, Márquez-Coello M, Cuesta-Sancho S, Girón-González JA. Similarities and differences between HIV and SARS-CoV-2. Int J Med Sci. 2021;18(3):846.10.7150/ijms.50133Search in Google Scholar PubMed PubMed Central

[5] Piai A, Fu Q, Sharp AK, Bighi B, Brown AM, Chou JJ. NMR Model of the Entire Membrane-Interacting Region of the HIV-1 Fusion Protein and Its Perturbation of Membrane Morphology. J Am Chem Soc. 2021;143(17):6609–15.10.1021/jacs.1c01762Search in Google Scholar PubMed

[6] Boily M-C, Baggaley RF, Wang L, Masse B, White RG, Hayes RJ, et al. Heterosexual risk of HIV-1 infection per sexual act: Systematic review and meta-analysis of observational studies. Lancet Infect Dis. 2009;9(2):118–29.10.1016/S1473-3099(09)70021-0Search in Google Scholar PubMed PubMed Central

[7] Baggaley RF, Boily M-C, White RG, Alary M. Risk of HIV-1 transmission for parenteral exposure and blood transfusion: A systematic review and meta-analysis. Aids. 2006;20(6):805–12.10.1097/01.aids.0000218543.46963.6dSearch in Google Scholar PubMed

[8] Amin O, Powers J, Bricker KM, Chahroudi A. Understanding viral and immune interplay during vertical transmission of HIV: Implications for cure. Front Immunol. 2021;12:757400.10.3389/fimmu.2021.757400Search in Google Scholar PubMed PubMed Central

[9] Chen Z, Julg B. Therapeutic vaccines for the treatment of HIV. Transl Res. 2020;223:61–75.10.1016/j.trsl.2020.04.008Search in Google Scholar PubMed PubMed Central

[10] Bailon L, Mothe B, Berman L, Brander C. Novel approaches towards a functional cure of HIV/AIDS. Drugs. 2020;80(9):859–68.10.1007/s40265-020-01322-ySearch in Google Scholar PubMed PubMed Central

[11] Mothe B, Rosás-Umbert M, Coll P, Manzardo C, Puertas MC, Morón-López S, et al. HIVconsv vaccines and romidepsin in early-treated HIV-1-infected individuals: Safety, immunogenicity and effect on the viral reservoir (Study BCN02). Front immunol. 2020;11:823.10.3389/fimmu.2020.00823Search in Google Scholar PubMed PubMed Central

[12] Webster RG, Monto AS, Braciale TJ, Lamb RA. Textbook of influenza. Germany: Wiley; 2014.10.1002/9781118636817Search in Google Scholar

[13] Dadonaite B, Gilbertson B, Knight ML, Trifkovic S, Rockman S, Laederach A, et al. The structure of the influenza A virus genome. Nat Microbiol. 2019;4(11):1781–9.10.1038/s41564-019-0513-7Search in Google Scholar PubMed PubMed Central

[14] Brankston G, Gitterman L, Hirji Z, Lemieux C, Gardam M. Transmission of influenza A in human beings. Lancet Infect Dis. 2007;7(4):257–65.10.1016/S1473-3099(07)70029-4Search in Google Scholar PubMed

[15] Monto AS, Gravenstein S, Elliott M, Colopy M, Schweinle J. Clinical signs and symptoms predicting influenza infection. Arch Intern Med. 2000;160(21):3243–7.10.1001/archinte.160.21.3243Search in Google Scholar PubMed

[16] Sivanandy P, Xien FZ, Kit LW, Wei YT, En KH, Lynn LC. A review on current trends in the treatment of human infection with H7N9-avian influenza A. J Infect public health. 2019;12(2):153–8.10.1016/j.jiph.2018.08.005Search in Google Scholar PubMed

[17] Marty AM, Jones MK. The novel coronavirus (SARS-CoV-2) is a one health issue. One Health. 2020;9:100123.10.1016/j.onehlt.2020.100123Search in Google Scholar PubMed PubMed Central

[18] Velavan TP, Meyer CG. The COVID‐19 epidemic. Trop Med Int Health. 2020;25(3):278.10.1111/tmi.13383Search in Google Scholar PubMed PubMed Central

[19] Wille M, Holmes EC. Wild birds as reservoirs for diverse and abundant gamma-and deltacoronaviruses. FEMS Microbiol Rev. 2020;44(5):631–44.10.1093/femsre/fuaa026Search in Google Scholar PubMed PubMed Central

[20] Weiss C, Carriere M, Fusco L, Capua I, Regla-Nava JA, Pasquali M, et al. Toward nanotechnology-enabled approaches against the COVID-19 pandemic. ACS Nano. 2020;14(6):6383–406.10.1021/acsnano.0c03697Search in Google Scholar PubMed PubMed Central

[21] Tao K, Tzou PL, Nouhin J, Gupta RK, de Oliveira T, Kosakovsky Pond SL, et al. The biological and clinical significance of emerging SARS-CoV-2 variants. Nat Rev Genet. 2021;22(12):757–73.10.1038/s41576-021-00408-xSearch in Google Scholar PubMed PubMed Central

[22] Izumi H, Nafie LA, Dukor RK. Conformational variability correlation prediction of transmissibility and neutralization escape ability for multiple mutation SARS-CoV-2 strains using SSSCPreds. ACS Omega. 2021;6(29):19323–9.10.1021/acsomega.1c03055Search in Google Scholar PubMed PubMed Central

[23] Zhao S, Ran J, Han L. Exploring the interaction between E484K and N501Y substitutions of SARS-CoV-2 in shaping the transmission advantage of COVID-19 in Brazil: A Modeling Study. Am J Trop Med Hyg. 2021;105(5):1247.10.4269/ajtmh.21-0412Search in Google Scholar PubMed PubMed Central

[24] Tegally H, Wilkinson E, Giovanetti M, Iranzadeh A, Fonseca V, Giandhari J, et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature. 2021;592(7854):438–43.10.1038/s41586-021-03402-9Search in Google Scholar PubMed

[25] Volz E, Mishra S, Chand M, Barrett JC, Johnson R, Geidelberg L, et al. Assessing transmissibility of SARS-CoV-2 lineage B. 1.1. 7 in England. Nature. 2021;593(7858):266–9.10.1038/s41586-021-03470-xSearch in Google Scholar PubMed

[26] Davies NG, Jarvis CI, Edmunds WJ, Jewell NP, Diaz-Ordaz K, Keogh RH. Increased mortality in community-tested cases of SARS-CoV-2 lineage B. 1.1. 7. Nature. 2021;593(7858):270–4.10.1038/s41586-021-03426-1Search in Google Scholar PubMed PubMed Central

[27] Hart WS, Miller E, Andrews NJ, Waight P, Maini PK, Funk S, et al. Generation time of the alpha and delta SARS-CoV-2 variants: An epidemiological analysis. Lancet Infect Dis. 2022;22(5):603–10.10.1016/S1473-3099(22)00001-9Search in Google Scholar PubMed PubMed Central

[28] Dhar MS, Marwal R, Vs R, Ponnusamy K, Jolly B, Bhoyar RC, et al. Genomic characterization and epidemiology of an emerging SARS-CoV-2 variant in Delhi, India. Science. 2021;374(6570):995–9.10.1126/science.abj9932Search in Google Scholar PubMed PubMed Central

[29] McCallum M, Walls AC, Sprouse KR, Bowen JE, Rosen LE, Dang HV, et al. Molecular basis of immune evasion by the Delta and Kappa SARS-CoV-2 variants. Science. 2021;374(6575):1621–6.10.1126/science.abl8506Search in Google Scholar PubMed

[30] Faria NR, Mellan TA, Whittaker C, Claro IM, Candido DD, Mishra S, et al. Genomics and epidemiology of the P. 1 SARS-CoV-2 lineage in Manaus, Brazil. Science. 2021;372(6544):815–21.10.1126/science.abh2644Search in Google Scholar PubMed PubMed Central

[31] Duerr R, Dimartino D, Marier C, Zappile P, Wang G, Lighter J, et al. Dominance of Alpha and Iota variants in SARS-CoV-2 vaccine breakthrough infections in New York City. J Clin Investigation. 2021;131(18):1.10.1172/JCI152702Search in Google Scholar PubMed PubMed Central

[32] Alizon S, Haim-Boukobza S, Foulongne V, Verdurme L, Trombert-Paolantoni S, Lecorche E, et al. Rapid spread of the SARS-CoV-2 Delta variant in some French regions, June 2021. Eurosurveillance. 2021;26(28):2100573.10.2807/1560-7917.ES.2021.26.28.2100573Search in Google Scholar PubMed PubMed Central

[33] Acevedo ML, Alonso-Palomares L, Bustamante A, Gaggero A, Paredes F, Cortés CP, et al. Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda. MedRxiv. 2021.10.1101/2021.06.28.21259673Search in Google Scholar

[34] Davies NG, Abbott S, Barnard RC, Jarvis CI, Kucharski AJ, Munday JD, et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B. 1.1. 7 in England. Science. 2021;372(6538):eabg3055.10.1126/science.abg3055Search in Google Scholar PubMed PubMed Central

[35] Xie X, Han J-B, Ma G, Feng X-L, Li X, Zou Q-C, et al. Emerging SARS-CoV-2 B. 1.621/Mu variant is prominently resistant to inactivated vaccine-elicited antibodies. Zool Res. 2021;42(6):789.10.24272/j.issn.2095-8137.2021.343Search in Google Scholar PubMed PubMed Central

[36] Ghosh N, Nandi S, Saha I. A review on evolution of emerging SARS-CoV-2 variants based on spike glycoprotein. Int Immunopharmacol. 2022;105:108565.10.1016/j.intimp.2022.108565Search in Google Scholar PubMed PubMed Central

[37] Langone M, Petta L, Cellamare C, Ferraris M, Guzzinati R, Mattioli D, et al. SARS-CoV-2 in water services: Presence and impacts. Environ Pollut. 2021;268:115806.10.1016/j.envpol.2020.115806Search in Google Scholar PubMed PubMed Central

[38] Asadi S, Bouvier N, Wexler AS, Ristenpart WD. The coronavirus pandemic and aerosols: Does COVID-19 transmit via expiratory particles?. Aerosol Sci Technol; 2020;54(6):635–8.10.1080/02786826.2020.1749229Search in Google Scholar PubMed PubMed Central

[39] Yépiz-Gómez MS, Gerba CP, Bright KR. Survival of respiratory viruses on fresh produce. Food Environ Virol. 2013;5(3):150–6.10.1007/s12560-013-9114-4Search in Google Scholar PubMed PubMed Central

[40] McKinney KR, Gong YY, Lewis TG. Environmental transmission of SARS at Amoy Gardens. J Environ Health. 2006;68(9):26.Search in Google Scholar

[41] Amirian ES. Potential fecal transmission of SARS-CoV-2: Current evidence and implications for public health. Int J Infect Dis. 2020;95:363–70.10.1016/j.ijid.2020.04.057Search in Google Scholar PubMed PubMed Central

[42] Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020;158(6):1831–3.e3.10.1053/j.gastro.2020.02.055Search in Google Scholar PubMed PubMed Central

[43] Du L, Yang Y, Zhang X, Li F. Recent advances in nanotechnology-based COVID-19 vaccines and therapeutic antibodies. Nanoscale. 2022;14(4):1054–74.10.1039/D1NR03831ASearch in Google Scholar PubMed PubMed Central

[44] Palestino G, García-Silva I, González-Ortega O, Rosales-Mendoza S. Can nanotechnology help in the fight against COVID-19? Expert Rev Anti-Infect Ther. 2020;18(9):849–64.10.1080/14787210.2020.1776115Search in Google Scholar PubMed

[45] Rai M, Bonde S, Yadav A, Bhowmik A, Rathod S, Ingle P, et al. Nanotechnology as a shield against COVID-19: Current advancement and limitations. Viruses. 2021;13(7):1224.10.3390/v13071224Search in Google Scholar PubMed PubMed Central

[46] Motiei M, Aboutalebi F, Forouzanfar M, Dormiani K, Nasr-Esfahani MH, Mirahmadi-Zare SZ. Smart co-delivery of miR-34a and cytotoxic peptides (LTX-315 and melittin) by chitosan based polyelectrolyte nanocarriers for specific cancer cell death induction. Mater Sci Eng C. 2021;128:112258.10.1016/j.msec.2021.112258Search in Google Scholar PubMed

[47] Tsang HF, Chan LWC, Cho WCS, Yu ACS, Yim AKY, Chan AKC, et al. An update on COVID-19 pandemic: The epidemiology, pathogenesis, prevention and treatment strategies. Expert Rev Anti-Infect Ther. 2021;19(7):877–88.10.1080/14787210.2021.1863146Search in Google Scholar PubMed

[48] Mao L, Chen Z, Wang Y, Chen C. Design and application of nanoparticles as vaccine adjuvants against human corona virus infection. J Inorg Biochem. 2021;219:111454.10.1016/j.jinorgbio.2021.111454Search in Google Scholar PubMed PubMed Central

[49] Duan Y, Wang S, Zhang Q, Gao W, Zhang L. Nanoparticle approaches against SARS-CoV-2 infection. Curr OpSolid State Mater Sci. 2021;25(6):100964.10.1016/j.cossms.2021.100964Search in Google Scholar PubMed PubMed Central

[50] Pati R, Shevtsov M, Sonawane A. Nanoparticle vaccines against infectious diseases. Front Immunology. 2018;9:2224.10.3389/fimmu.2018.02224Search in Google Scholar PubMed PubMed Central

[51] Zhang N, Li C, Jiang S, Du L. Recent advances in the development of virus-like particle-based flavivirus vaccines. Vaccines. 2020;8(3):481.10.3390/vaccines8030481Search in Google Scholar PubMed PubMed Central

[52] Zhang N-N, Li X-F, Deng Y-Q, Zhao H, Huang Y-J, Yang G, et al. A thermostable mRNA vaccine against COVID-19. Cell. 2020;182(5):1271–83.e16.10.1016/j.cell.2020.07.024Search in Google Scholar PubMed PubMed Central

[53] Laczkó D, Hogan MJ, Toulmin SA, Hicks P, Lederer K, Gaudette BT, et al. A single immunization with nucleoside-modified mRNA vaccines elicits strong cellular and humoral immune responses against SARS-CoV-2 in mice. Immunity. 2020;53(4):724–32.e7.10.1016/j.immuni.2020.07.019Search in Google Scholar PubMed PubMed Central

[54] Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603–15.10.1056/NEJMoa2034577Search in Google Scholar PubMed PubMed Central

[55] Walsh EE, Frenck Jr RW, Falsey AR, Kitchin N, Absalon J, Gurtman A, et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med. 2020;383(25):2439–50.10.1056/NEJMoa2027906Search in Google Scholar PubMed PubMed Central

[56] Kaiser RA, Haller MC, Apfalter P, Kerschner H, Cejka D. Comparison of BNT162b2 (Pfizer–BioNtech) and mRNA-1273 (Moderna) SARS-CoV-2 mRNA vaccine immunogenicity in dialysis patients. Kidney Int. 2021;100(3):697–8.10.1016/j.kint.2021.07.004Search in Google Scholar PubMed PubMed Central

[57] Huang WC, Zhou S, He X, Chiem K, Mabrouk MT, Nissly RH, et al. SARS‐CoV‐2 RBD neutralizing antibody induction is enhanced by particulate vaccination. Adv Mater. 2020;32(50):2005637.10.1002/adma.202005637Search in Google Scholar PubMed PubMed Central

[58] Peng S, Cao F, Xia Y, Gao XD, Dai L, Yan J, et al. Particulate alum via pickering emulsion for an enhanced COVID‐19 vaccine adjuvant. Adv Mater. 2020;32(40):2004210.10.1002/adma.202004210Search in Google Scholar PubMed

[59] Wang N, Shang J, Jiang S, Du L. Subunit vaccines against emerging pathogenic human coronaviruses. Front Microbiol. 2020;11:298.10.3389/fmicb.2020.00298Search in Google Scholar PubMed PubMed Central

[60] Kanekiyo M, Wei C-J, Yassine HM, McTamney PM, Boyington JC, Whittle JR, et al. Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature. 2013;499(7456):102–6.10.1038/nature12202Search in Google Scholar PubMed PubMed Central

[61] Tokatlian T, Read BJ, Jones CA, Kulp DW, Menis S, Chang JY, et al. Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers. Science. 2019;363(6427):649–54.10.1126/science.aat9120Search in Google Scholar PubMed PubMed Central

[62] Tan TK, Rijal P, Rahikainen R, Keeble AH, Schimanski L, Hussain S, et al. A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses. Nat Commun. 2021;12(1):1–16.10.1038/s41467-020-20654-7Search in Google Scholar PubMed PubMed Central

[63] Walls AC, Fiala B, Schäfer A, Wrenn S, Pham MN, Murphy M, et al. Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2. Cell. 2020;183(5):1367–82.e17.10.1016/j.cell.2020.10.043Search in Google Scholar PubMed PubMed Central

[64] Powell AE, Zhang K, Sanyal M, Tang S, Weidenbacher PA, Li S, et al. A single immunization with spike-functionalized ferritin vaccines elicits neutralizing antibody responses against SARS-CoV-2 in mice. ACS Cent Sci. 2021;7(1):183–99.10.1021/acscentsci.0c01405Search in Google Scholar PubMed PubMed Central

[65] Wang W, Huang B, Zhu Y, Tan W, Zhu M. Ferritin nanoparticle-based SARS-CoV-2 RBD vaccine induces a persistent antibody response and long-term memory in mice. Cell Mol Immunol. 2021;18(3):749–51.10.1038/s41423-021-00643-6Search in Google Scholar PubMed PubMed Central

[66] Saunders KO, Lee E, Parks R, Martinez DR, Li D, Chen H, et al. Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses. Nature. 2021;594(7864):553–9.10.1038/s41586-021-03594-0Search in Google Scholar PubMed PubMed Central

[67] Ma X, Zou F, Yu F, Li R, Yuan Y, Zhang Y, et al. Nanoparticle vaccines based on the receptor binding domain (RBD) and heptad repeat (HR) of SARS-CoV-2 elicit robust protective immune responses. Immunity. 2020;53(6):1315–30.e9.10.1016/j.immuni.2020.11.015Search in Google Scholar PubMed PubMed Central

[68] Huang X, Kon E, Han X, Zhang X, Kong N, Mitchell MJ, et al. Nanotechnology-based strategies against SARS-CoV-2 variants. Nat Nanotechnol. 2022;17(10):1027–37.10.1038/s41565-022-01174-5Search in Google Scholar PubMed

[69] Kumar N, Admane N, Kumari A, Sood D, Grover S, Prajapati VK, et al. Cytotoxic T-lymphocyte elicited vaccine against SARS-CoV-2 employing immunoinformatics framework. Sci Rep. 2021;11(1):1–14.10.1038/s41598-021-86986-6Search in Google Scholar PubMed PubMed Central

[70] Sahoo B, Kant K, Rai NK, Chaudhary DK. Identification of T-cell epitopes in proteins of novel human coronavirus, SARS-Cov-2 for vaccine development. Int J Appl Biol Pharm Technol. 2020;11(2):37–45.Search in Google Scholar

[71] Chan Y, Ng SW, Singh SK, Gulati M, Gupta G, Chaudhary SK, et al. Revolutionizing polymer-based nanoparticle-linked vaccines for targeting respiratory viruses: A perspective. Life Sci. 2021;280:119744.10.1016/j.lfs.2021.119744Search in Google Scholar PubMed PubMed Central

[72] Mohamed SH, Arafa AS, Mady WH, Fahmy HA, Omer LM, Morsi RE. Preparation and immunological evaluation of inactivated avian influenza virus vaccine encapsulated in chitosan nanoparticles. Biologicals. 2018;51:46–53.10.1016/j.biologicals.2017.10.004Search in Google Scholar PubMed

[73] Huang T, Song X, Jing J, Zhao K, Shen Y, Zhang X, et al. Chitosan-DNA nanoparticles enhanced the immunogenicity of multivalent DNA vaccination on mice against Trueperella pyogenes infection. J Nanobiotechnol. 2018;16(1):1–15.10.1186/s12951-018-0337-2Search in Google Scholar PubMed PubMed Central

[74] Verheul RJ, Slütter B, Bal SM, Bouwstra JA, Jiskoot W, Hennink WE. Covalently stabilized trimethyl chitosan-hyaluronic acid nanoparticles for nasal and intradermal vaccination. J Controlled Release. 2011;156(1):46–52.10.1016/j.jconrel.2011.07.014Search in Google Scholar PubMed

[75] Yu H, Lin H, Xie Y, Qu M, Jiang M, Shi J, et al. MUC1 vaccines using β-cyclodextrin grafted chitosan (CS–g–CD) as carrier via host-guest interaction elicit robust immune responses. Chin Chem Lett. 2022;33(11):4882–5.10.1016/j.cclet.2022.02.072Search in Google Scholar

[76] Rocha CE, Silva MF, Guedes AC, Carvalho TP, Eckstein C, Ribeiro NQ, et al. Alginate-chitosan microcapsules improve vaccine potential of gamma-irradiated Listeria monocytogenes against listeriosis in murine model. Int J Biol Macromolecules. 2021;176:567–77.10.1016/j.ijbiomac.2021.02.056Search in Google Scholar PubMed

[77] Stiepel RT, Batty CJ, MacRaild CA, Norton RS, Bachelder E, Ainslie KM. Merozoite surface protein 2 adsorbed onto acetalated dextran microparticles for malaria vaccination. Int J Pharmaceutics. 2021;593:120168.10.1016/j.ijpharm.2020.120168Search in Google Scholar PubMed

[78] Nakahashi-Ouchida R, Yuki Y, Kiyono H. Cationic pullulan nanogel as a safe and effective nasal vaccine delivery system for respiratory infectious diseases. Hum Vaccines Immunother. 2018;14(9):2189–93.10.1080/21645515.2018.1461298Search in Google Scholar PubMed PubMed Central

[79] Ferrell KC, Stewart EL, Counoupas C, Ashhurst TM, Britton WJ, Petrovsky N, et al. Intrapulmonary vaccination with delta-inulin adjuvant stimulates non-polarised chemotactic signalling and diverse cellular interaction. Mucosal Immunol. 2021;14(3):762–73.10.1038/s41385-021-00379-6Search in Google Scholar PubMed PubMed Central

[80] Bandeira AC, de Oliveira Matos A, Evangelista BS, da Silva SM, Nagib PRA, de Moraes Crespo A, et al. Is it possible to track intracellular chitosan nanoparticles using magnetic nanoparticles as contrast agent? Bioorg Med Chem. 2019;27(12):2637–43.10.1016/j.bmc.2019.04.011Search in Google Scholar PubMed

[81] Hiremath J, Kang K-I, Xia M, Elaish M, Binjawadagi B, Ouyang K, et al. Entrapment of H1N1 influenza virus derived conserved peptides in PLGA nanoparticles enhances T cell response and vaccine efficacy in pigs. PLoS One. 2016;11(4):e0151922.10.1371/journal.pone.0151922Search in Google Scholar PubMed PubMed Central

[82] Singh J, Pandit S, Bramwell VW, Alpar HO. Diphtheria toxoid loaded poly-(ε-caprolactone) nanoparticles as mucosal vaccine delivery systems. Methods. 2006;38(2):96–105.10.1016/j.ymeth.2005.11.003Search in Google Scholar PubMed

[83] Zhang D, Atochina-Vasserman EN, Maurya DS, Liu M, Xiao Q, Lu J, et al. Targeted delivery of mRNA with one-component ionizable amphiphilic janus dendrimers. J Am Chem Soc. 2021;143(43):17975–82.10.1021/jacs.1c09585Search in Google Scholar PubMed

[84] Ren S, Guo L, Wang C, Ru J, Yang Y, Wang Y, et al. Construction of an effective delivery system for DNA vaccines using biodegradable polylactic acid based microspheres. J Biomed Nanotechnol. 2021;17(5):971–80.10.1166/jbn.2021.3081Search in Google Scholar PubMed

[85] Stephens LM, Ross KA, Waldstein KA, Legge KL, McLellan JS, Narasimhan B, et al. Prefusion F–based polyanhydride nanovaccine induces both humoral and cell-mediated immunity resulting in long-lasting protection against respiratory syncytial virus. J Immunol. 2021;206(9):2122–34.10.4049/jimmunol.2100018Search in Google Scholar PubMed PubMed Central

[86] Klimek L, Novak N, Cabanillas B, Jutel M, Bousquet J, Akdis CA. Allergenic components of the mRNA‐1273 vaccine for COVID‐19: Possible involvement of polyethylene glycol and IgG‐mediated complement activation. Allergy. 2021;76(11):3307–13.10.1111/all.14794Search in Google Scholar PubMed PubMed Central

[87] Guo S, Fu D, Utupova A, Sun D, Zhou M, Jin Z, et al. Applications of polymer-based nanoparticles in vaccine field. Nanotechnol Rev. 2019;8(1):143–55.10.1515/ntrev-2019-0014Search in Google Scholar

[88] Hess KL, Medintz IL, Jewell CM. Designing inorganic nanomaterials for vaccines and immunotherapies. Nano Today. 2019;27:73–98.10.1016/j.nantod.2019.04.005Search in Google Scholar PubMed PubMed Central

[89] Zhou Q, Zhang Y, Du J, Li Y, Zhou Y, Fu Q, et al. Different-sized gold nanoparticle activator/antigen increases dendritic cells accumulation in liver-draining lymph nodes and CD8 + T cell responses. ACS Nano. 2016;10(2):2678–92.10.1021/acsnano.5b07716Search in Google Scholar PubMed

[90] Hu Z, Song B, Xu L, Zhong Y, Peng F, Ji X, et al. Aqueous synthesized quantum dots interfere with the NF-κB pathway and confer anti-tumor, anti-viral and anti-inflammatory effects. Biomaterials. 2016;108:187–96.10.1016/j.biomaterials.2016.08.047Search in Google Scholar PubMed

[91] Versiani AF, Astigarraga RG, Rocha ES, Barboza APM, Kroon EG, Rachid MA, et al. Multi-walled carbon nanotubes functionalized with recombinant Dengue virus 3 envelope proteins induce significant and specific immune responses in mice. J Nanobiotechnol. 2017;15(1):1–13.10.1186/s12951-017-0259-4Search in Google Scholar PubMed PubMed Central

[92] Pescatori M, Bedognetti D, Venturelli E, Ménard-Moyon C, Bernardini C, Muresu E, et al. Functionalized carbon nanotubes as immunomodulator systems. Biomaterials. 2013;34(18):4395–403.10.1016/j.biomaterials.2013.02.052Search in Google Scholar PubMed

[93] Qiao L, Chen M, Li S, Hu J, Gong C, Zhang Z, et al. A peptide-based subunit candidate vaccine against SARS-CoV-2 delivered by biodegradable mesoporous silica nanoparticles induced high humoral and cellular immunity in mice. Biomater Sci. 2021;9(21):7287–96.10.1039/D1BM01060CSearch in Google Scholar PubMed

[94] Motamedi‐sedeh F, Saboorizadeh A, Khalili I, Sharbatdaran M, Wijewardana V, Arbabi A. Carboxymethyl chitosan bounded iron oxide nanoparticles and gamma‐irradiated avian influenza subtype H9N2 vaccine to development of immunity on mouse and chicken. Vet Med Sci. 2021;8(2):626–34.10.1002/vms3.680Search in Google Scholar PubMed PubMed Central

[95] Orecchioni M, Bedognetti D, Newman L, Fuoco C, Spada F, Hendrickx W, et al. Single-cell mass cytometry and transcriptome profiling reveal the impact of graphene on human immune cells. Nat Commun. 2017;8(1):1–14.10.1038/s41467-017-01015-3Search in Google Scholar PubMed PubMed Central

[96] Xu L, Xiang J, Liu Y, Xu J, Luo Y, Feng L, et al. Functionalized graphene oxide serves as a novel vaccine nano-adjuvant for robust stimulation of cellular immunity. Nanoscale. 2016;8(6):3785–95.10.1039/C5NR09208FSearch in Google Scholar

[97] Bilyy R, Pagneux Q, François N, Bila G, Grytsko R, Lebedin Y, et al. Rapid generation of coronaviral immunity using recombinant peptide modified nanodiamonds. Pathogens. 2021;10(7):861.10.3390/pathogens10070861Search in Google Scholar PubMed PubMed Central

[98] Cao W, He L, Cao W, Huang X, Jia K, Dai J. Recent progress of graphene oxide as a potential vaccine carrier and adjuvant. Acta biomaterialia. 2020;112:14–28.10.1016/j.actbio.2020.06.009Search in Google Scholar PubMed

[99] Bakkar MR, Faraag AHI, Soliman ER, Fouda MS, Sarguos AMM, McLean GR, et al. Rhamnolipids nano-micelles as a potential hand sanitizer. Antibiotics. 2021;10(7):751.10.3390/antibiotics10070751Search in Google Scholar PubMed PubMed Central

[100] Monge FA, Jagadesan P, Bondu V, Donabedian PL, Ista L, Chi EY, et al. Highly effective inactivation of SARS-CoV-2 by conjugated polymers and oligomers. ACS Appl Mater Interfaces. 2020;12(50):55688–95.10.1021/acsami.0c17445Search in Google Scholar PubMed PubMed Central

[101] Chowdhury MA, Shuvho MBA, Shahid MA, Haque AM, Kashem MA, Lam SS, et al. Prospect of biobased antiviral face mask to limit the coronavirus outbreak. Environ Res. 2021;192:110294.10.1016/j.envres.2020.110294Search in Google Scholar PubMed PubMed Central

[102] Zhong H, Zhu Z, Lin J, Cheung CF, Lu VL, Yan F, et al. Reusable and recyclable graphene masks with outstanding superhydrophobic and photothermal performances. ACS nano. 2020;14(5):6213–21.10.1021/acsnano.0c02250Search in Google Scholar PubMed

[103] Kasbe PS, Gade H, Liu S, Chase GG, Xu W. Ultrathin polydopamine-graphene oxide hybrid coatings on polymer filters with improved filtration performance and functionalities. ACS Appl Bio Mater. 2021;4(6):5180–8.10.1021/acsabm.1c00367Search in Google Scholar PubMed

[104] Gopal V, Nilsson-Payant BE, French H, Siegers JY, Yung W-S, Hardwick M, et al. Zinc-embedded polyamide fabrics inactivate SARS-CoV-2 and influenza a virus. ACS Appl Mater Interfaces. 2021;13(26):30317–25.10.1021/acsami.1c04412Search in Google Scholar PubMed PubMed Central

[105] Jung S, Yang J-Y, Byeon E-Y, Kim D-G, Lee D-G, Ryoo S, et al. Copper-coated polypropylene filter face mask with SARS-COV-2 antiviral ability. Polymers. 2021;13(9):1367.10.3390/polym13091367Search in Google Scholar PubMed PubMed Central

[106] Joe YH, Park DH, Hwang J. Evaluation of Ag nanoparticle coated air filter against aerosolized virus: Anti-viral efficiency with dust loading. J Hazard Mater. 2016;301:547–53.10.1016/j.jhazmat.2015.09.017Search in Google Scholar PubMed PubMed Central

[107] Kumar A, Sharma A, Chen Y, Jones MM, Vanyo ST, Li C, et al. Copper@ ZIF‐8 core‐shell nanowires for reusable antimicrobial face masks. Adv Funct Mater. 2021;31(10):2008054.10.1002/adfm.202008054Search in Google Scholar PubMed PubMed Central

[108] Balagna C, Perero S, Percivalle E, Nepita EV, Ferraris M. Virucidal effect against coronavirus SARS-CoV-2 of a silver nanocluster/silica composite sputtered coating. Open Ceram. 2020;1:100006.10.1016/j.oceram.2020.100006Search in Google Scholar

[109] Abbas WA, Shaheen BS, Ghanem LG, Badawy IM, Abodouh MM, Abdou SM, et al. Cost-effective face mask filter based on hybrid composite nanofibrous layers with high filtration efficiency. Langmuir. 2021;37(24):7492–502.10.1021/acs.langmuir.1c00926Search in Google Scholar PubMed

[110] Kumar S, Karmacharya M, Joshi SR, Gulenko O, Park J, Kim G-H, et al. Photoactive antiviral face mask with self-sterilization and reusability. Nano Lett. 2020;21(1):337–43.10.1021/acs.nanolett.0c03725Search in Google Scholar PubMed

[111] He R, Li J, Chen M, Zhang S, Cheng Y, Ning X, et al. Tailoring moisture electroactive Ag/Zn@ cotton coupled with electrospun PVDF/PS nanofibers for antimicrobial face masks. J Hazard Mater. 2022;428:128239.10.1016/j.jhazmat.2022.128239Search in Google Scholar PubMed

[112] Ciejka J, Wolski K, Nowakowska M, Pyrc K, Szczubiałka K. Biopolymeric nano/microspheres for selective and reversible adsorption of coronaviruses. Mater Sci Eng C. 2017;76:735–42.10.1016/j.msec.2017.03.047Search in Google Scholar PubMed PubMed Central

[113] Gupta I, Chakraborty J, Roy S, Farinas ET, Mitra S. Nanocarbon immobilized membranes for generating bacteria and endotoxin free water via membrane distillation. Sep Purif Technol. 2021;259:118133.10.1016/j.seppur.2020.118133Search in Google Scholar

[114] Zheng X, Shen Z-P, Cheng C, Shi L, Cheng R, Yuan D-H. Photocatalytic disinfection performance in virus and virus/bacteria system by Cu-TiO2 nanofibers under visible light. Environ Pollut. 2018;237:452–9.10.1016/j.envpol.2018.02.074Search in Google Scholar PubMed

[115] Kusiak-Nejman E, Morawski AW. TiO2/graphene-based nanocomposites for water treatment: A brief overview of charge carrier transfer, antimicrobial and photocatalytic performance. Appl Catal B Environ. 2019;253:179–86.10.1016/j.apcatb.2019.04.055Search in Google Scholar

[116] Liu H, Huang J, Mao J, Chen Z, Chen G, Lai Y. Transparent antibacterial nanofiber air filters with highly efficient moisture resistance for sustainable particulate matter capture. Iscience. 2019;19:214–23.10.1016/j.isci.2019.07.020Search in Google Scholar PubMed PubMed Central

[117] Stanford MG, Li JT, Chen Y, McHugh EA, Liopo A, Xiao H, et al. Self-sterilizing laser-induced graphene bacterial air filter. ACS nano. 2019;13(10):11912–20.10.1021/acsnano.9b05983Search in Google Scholar PubMed

[118] Sun W-H, Hui L-F, Yang Q, Zhao G-D. Nanofiltration filter paper based on multi-walled carbon nanotubes and cellulose filter papers. RSC Adv. 2021;11(2):1194–9.10.1039/D0RA08585ESearch in Google Scholar

[119] Deshmukh SP, Patil S, Mullani S, Delekar S. Silver nanoparticles as an effective disinfectant: A review. Mater Sci Eng C. 2019;97:954–65.10.1016/j.msec.2018.12.102Search in Google Scholar PubMed PubMed Central

[120] Ko Y-S, Joe YH, Seo M, Lim K, Hwang J, Woo K. Prompt and synergistic antibacterial activity of silver nanoparticle-decorated silica hybrid particles on air filtration. J Mater Chem B. 2014;2(39):6714–22.10.1039/C4TB01068JSearch in Google Scholar

[121] Han J, Chen L, Duan S-M, Yang Q-X, Yang M, Gao C, et al. Efficient and quick inactivation of SARS coronavirus and other microbes exposed to the surfaces of some metal catalysts. Biomed Environ Sci BES. 2005;18(3):176–80.Search in Google Scholar

[122] Wang I-J, Chen Y-C, Su C, Tsai M-H, Shen W-T, Bai C-H, et al. Effectiveness of the Nanosilver/TiO2-chitosan antiviral filter on the removal of viral aerosols. J Aerosol Med Pulm Drug Delivery. 2021;34(5):293–302.10.1089/jamp.2020.1607Search in Google Scholar PubMed

[123] Heo KJ, Jeong SB, Shin J, Hwang GB, Ko HS, Kim Y, et al. Water-repellent TiO2-organic dye-based air filters for efficient visible-light-activated photochemical inactivation against bioaerosols. Nano Lett. 2020;21(4):1576–83.10.1021/acs.nanolett.0c03173Search in Google Scholar PubMed

[124] Lv D, Wang R, Tang G, Mou Z, Lei J, Han J, et al. Ecofriendly electrospun membranes loaded with visible-light-responding nanoparticles for multifunctional usages: Highly efficient air filtration, dye scavenging, and bactericidal activity. ACS Appl Mater Interfaces. 2019;11(13):12880–9.10.1021/acsami.9b01508Search in Google Scholar PubMed

[125] Milewska A, Chi Y, Szczepanski A, Barreto-Duran E, Liu K, Liu D, et al. HTCC as a highly effective polymeric inhibitor of SARS-CoV-2 and MERS-CoV. BioRxiv. 2020.10.1101/2020.03.29.014183Search in Google Scholar

[126] Khaiboullina S, Uppal T, Dhabarde N, Subramanian VR, Verma SC. Inactivation of human coronavirus by titania nanoparticle coatings and UVC radiation: Throwing light on SARS-CoV-2. Viruses. 2020;13(1):19.10.3390/v13010019Search in Google Scholar PubMed PubMed Central

[127] Jeremiah SS, Miyakawa K, Morita T, Yamaoka Y, Ryo A. Potent antiviral effect of silver nanoparticles on SARS-CoV-2. Biochemical biophysical Res Commun. 2020;533(1):195–200.10.1016/j.bbrc.2020.09.018Search in Google Scholar PubMed PubMed Central

[128] Zhu P, Wang Y, Chu H, Wang L. Superhydrophobicity preventing surface contamination as a novel strategy against COVID-19. J Colloid Interface Sci. 2021;600:613–9.10.1016/j.jcis.2021.05.031Search in Google Scholar PubMed PubMed Central

[129] Hamouda T, Ibrahim HM, Kafafy H, Mashaly H, Mohamed NH, Aly NM. Preparation of cellulose-based wipes treated with antimicrobial and antiviral silver nanoparticles as novel effective high-performance coronavirus fighter. Int J Biol macromolecules. 2021;181:990–1002.10.1016/j.ijbiomac.2021.04.071Search in Google Scholar PubMed PubMed Central

[130] Behzadinasab S, Chin A, Hosseini M, Poon L, Ducker WA. A surface coating that rapidly inactivates SARS-CoV-2. ACS Appl Mater Interfaces. 2020;12(31):34723–7.10.1021/acsami.0c11425Search in Google Scholar PubMed PubMed Central

[131] Asadi S, Bouvier N, Wexler AS, Ristenpart WD. The coronavirus pandemic and aerosols: Does COVID-19 transmit via expiratory particles?. Aerosol Sci Technol; 2020;54(6):635–8.10.1080/02786826.2020.1749229Search in Google Scholar PubMed PubMed Central

[132] Mallakpour S, Azadi E, Hussain CM. Fabrication of air filters with advanced filtration performance for removal of viral aerosols and control the spread of COVID-19. Adv Colloid Interface Sci. 2022;303:102653.10.1016/j.cis.2022.102653Search in Google Scholar PubMed PubMed Central

[133] Alghoraibi I, Alomari S. Different methods for nanofiber design and fabrication. Handbook of Nanofibers; 2018. p. 1–46.10.1007/978-3-319-42789-8_11-2Search in Google Scholar

[134] Bhattacharjee S, Joshi R, Yasir M, Adhikari A, Chughtai AA, Heslop D, et al. Graphene-and Nanoparticle-Embedded Antimicrobial and Biocompatible Cotton/Silk Fabrics for Protective Clothing. ACS Appl Bio Mater. 2021;4(8):6175–85.10.1021/acsabm.1c00508Search in Google Scholar PubMed

[135] Jeong SB, Lee DU, Lee BJ, Heo KJ, Kim DW, Hwang GB, et al. Photobiocidal-triboelectric nanolayer coating of photosensitizer/silica–alumina for reusable and visible-light-driven antibacterial/antiviral air filters. Chem Eng J. 2022;440:135830.10.1016/j.cej.2022.135830Search in Google Scholar PubMed PubMed Central

[136] Borkow G, Zhou SS, Page T, Gabbay J. A novel anti-influenza copper oxide containing respiratory face mask. PLoS One. 2010;5(6):e11295.10.1371/journal.pone.0011295Search in Google Scholar PubMed PubMed Central

[137] Karagoz S, Kiremitler NB, Sarp G, Pekdemir S, Salem S, Goksu AG, et al. Antibacterial, antiviral, and self-cleaning mats with sensing capabilities based on electrospun nanofibers decorated with ZnO nanorods and Ag nanoparticles for protective clothing applications. ACS Appl Mater Interfaces. 2021;13(4):5678–90.10.1021/acsami.0c15606Search in Google Scholar PubMed

[138] Lee B-Y, Behler K, Kurtoglu ME, Wynosky-Dolfi MA, Rest RF, Gogotsi Y. Titanium dioxide-coated nanofibers for advanced filters. J Nanopart Res. 2010;12(7):2511–9.10.1007/s11051-009-9820-xSearch in Google Scholar

[139] Ramaiah GB, Tegegne A, Melese B. Developments in nano-materials and analysing its role in fighting COVID-19. Mater Today Proc. 2021;47:4357–63.10.1016/j.matpr.2021.05.020Search in Google Scholar PubMed PubMed Central

[140] Phuna ZX, Panda BP, Hawala Shivashekaregowda NK, Madhavan P. Nanoprotection from SARS-COV-2: Would nanotechnology help in Personal Protection Equipment (PPE) to control the transmission of COVID-19? Int J Environ Health Res. 2022;1–30.10.1080/09603123.2022.2046710Search in Google Scholar PubMed

[141] Fibriana F, Amalia AV, Muntamah S, Ulva L, Aryanti S. Antimicrobial activities of green synthesized silver nanoparticles from Marchantia sp. extract: Testing an alcohol-free hand sanitizer product formula. J microbiol Biotechnol Food Sci. 2020;9(6):1034–8.10.15414/jmbfs.2020.9.6.1034-1038Search in Google Scholar

[142] Malabadi RB, Kolkar KP, Meti NT, Chalannavar RK. Role of plant based hand sanitizers during the recent outbreak of coronavirus (SARS-CoV-2) disease (Covid-19). Significances Bioeng Biosci. 2021;5(1):458–68.10.31031/SBB.2021.05.000605Search in Google Scholar

[143] Tran HN, Le GT, Nguyen DT, Juang R-S, Rinklebe J, Bhatnagar A, et al. SARS-CoV-2 coronavirus in water and wastewater: A critical review about presence and concern. Environ Res. 2021;193:110265.10.1016/j.envres.2020.110265Search in Google Scholar PubMed PubMed Central

[144] Romano-Bertrand S, Glele LA, Grandbastien B, Lepelletier D. Preventing SARS-CoV-2 transmission in rehabilitation pools and therapeutic water environments. J Hosp Infect. 2020;105(4):625–7.10.1016/j.jhin.2020.06.003Search in Google Scholar PubMed PubMed Central

[145] Rimoldi SG, Stefani F, Gigantiello A, Polesello S, Comandatore F, Mileto D, et al. Presence and infectivity of SARS-CoV-2 virus in wastewaters and rivers. Sci Total Environ. 2020;744:140911.10.1016/j.scitotenv.2020.140911Search in Google Scholar PubMed PubMed Central

[146] Nasir AM, Adam MR, Kamal SNEAM, Jaafar J, Othman MHD, Ismail AF, et al. A review of the potential of conventional and advanced membrane technology in the removal of pathogens from wastewater. Sep Purif Technol. 2022;286:120454.10.1016/j.seppur.2022.120454Search in Google Scholar PubMed PubMed Central

[147] Hardikar M, Ikner LA, Felix V, Presson LK, Rabe AB, Hickenbottom KL, et al. Membrane distillation provides a dual barrier for coronavirus and bacteriophage removal. Environ Sci Technol Lett. 2021;8(8):713–8.10.1021/acs.estlett.1c00483Search in Google Scholar

[148] Nthunya LN, Gutierrez L, Khumalo N, Derese S, Mamba BB, Verliefde AR, et al. Superhydrophobic PVDF nanofibre membranes coated with an organic fouling resistant hydrophilic active layer for direct-contact membrane distillation. Colloids Surf A. 2019;575:363–72.10.1016/j.colsurfa.2019.05.031Search in Google Scholar

[149] Biryukov J, Boydston JA, Dunning RA, Yeager JJ, Wood S, Ferris A, et al. SARS-CoV-2 is rapidly inactivated at high temperature. Environ Chem Lett. 2021;19(2):1773–7.10.1007/s10311-021-01187-xSearch in Google Scholar PubMed PubMed Central

[150] Soni V, Khosla A, Singh P, Nguyen V-H, Van Le Q, Selvasembian R, et al. Current perspective in metal oxide based photocatalysts for virus disinfection: A review. J Environ Manag. 2022;308:114617.10.1016/j.jenvman.2022.114617Search in Google Scholar PubMed PubMed Central

[151] Liu L, Meng G, Chen H, Wang C, Xue Y. Photocatalytic disinfection of different airborne microorganisms by TiO2/MXene filler: Inactivation efficiency, energy consumption and self-repair phenomenon. J Environ Chem Eng. 2022;10:107641.10.1016/j.jece.2022.107641Search in Google Scholar

[152] Nasir AM, Awang N, Hubadillah SK, Jaafar J, Othman MHD, Salleh WNW, et al. A review on the potential of photocatalysis in combatting SARS-CoV-2 in wastewater. J Water Process Eng. 2021;42:102111.10.1016/j.jwpe.2021.102111Search in Google Scholar PubMed PubMed Central

[153] Moor KJ, Valle DC, Li C, Kim J-H. Improving the visible light photoactivity of supported fullerene photocatalysts through the use of [C70] fullerene. Environ Sci Technol. 2015;49(10):6190–7.10.1021/es505888dSearch in Google Scholar PubMed

[154] Banerjee I, Douaisi MP, Mondal D, Kane RS. Light-activated nanotube–porphyrin conjugates as effective antiviral agents. Nanotechnology. 2012;23(10):105101.10.1088/0957-4484/23/10/105101Search in Google Scholar PubMed

[155] Łoczechin A, Séron K, Barras A, Giovanelli E, Belouzard S, Chen Y-T, et al. Functional carbon quantum dots as medical countermeasures to human coronavirus. ACS Appl Mater Interfaces. 2019;11(46):42964–74.10.1021/acsami.9b15032Search in Google Scholar PubMed PubMed Central

[156] Zhang C, Li Y, Wang C, Zheng X. Different inactivation behaviors and mechanisms of representative pathogens (Escherichia coli bacteria, human adenoviruses and Bacillus subtilis spores) in g-C3N4-based metal-free visible-light-enabled photocatalytic disinfection. Sci Total Environ. 2021;755:142588.10.1016/j.scitotenv.2020.142588Search in Google Scholar PubMed PubMed Central

[157] Shi Y, Huang J, Zeng G, Cheng W, Hu J. Photocatalytic membrane in water purification: Is it stepping closer to be driven by visible light? J Membr Sci. 2019;584:364–92.10.1016/j.memsci.2019.04.078Search in Google Scholar

[158] Doremalen NV, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020;382(16):1564–7.10.1056/NEJMc2004973Search in Google Scholar PubMed PubMed Central

[159] Vaze N, Pyrgiotakis G, McDevitt J, Mena L, Melo A, Bedugnis A, et al. Inactivation of common hospital acquired pathogens on surfaces and in air utilizing engineered water nanostructures (EWNS) based nano-sanitizers. Nanomedicine Nanotechnol Biol Med. 2019;18:234–42.10.1016/j.nano.2019.03.003Search in Google Scholar PubMed PubMed Central

[160] Ereth M, Fine J, Stamatatos F, Mathew B, Hess D, Simpser E. Healthcare-associated infection impact with bioaerosol treatment and COVID-19 mitigation measures. J Hosp Infect. 2021;116:69–77.10.1016/j.jhin.2021.07.006Search in Google Scholar PubMed PubMed Central

[161] Blocken B, van Druenen T, Ricci A, Kang L, van Hooff T, Qin P, et al. Ventilation and air cleaning to limit aerosol particle concentrations in a gym during the COVID-19 pandemic. Build Environ. 2021;193:107659.10.1016/j.buildenv.2021.107659Search in Google Scholar PubMed PubMed Central

[162] Yoon K-Y, Byeon JH, Park J-H, Ji JH, Bae GN, Hwang J. Antimicrobial characteristics of silver aerosol nanoparticles against Bacillus subtilis bioaerosols. Environ Eng Sci. 2008;25(2):289–94.10.1089/ees.2007.0003Search in Google Scholar

[163] Fan X, Rong L, Kong L, Li Y, Huang J, Cao Y, et al. Tug-of-war-inspired bio-based air filters with advanced filtration performance. ACS Appl Mater Interfaces. 2021;13(7):8736–44.10.1021/acsami.0c20596Search in Google Scholar PubMed

[164] Patial S, Kumar A, Raizada P, Van Le Q, Selvasembian R, Singh P, et al. Potential of Graphene based photocatalyst for antiviral activity with emphasis on COVID-19: A review. J Environ Chem Eng. 2022;10:107527.10.1016/j.jece.2022.107527Search in Google Scholar PubMed PubMed Central

[165] Lim ME, Lee Y-L, Zhang Y, Chu JJH. Photodynamic inactivation of viruses using upconversion nanoparticles. Biomaterials. 2012;33(6):1912–20.10.1016/j.biomaterials.2011.11.033Search in Google Scholar PubMed

[166] Kaiser J-P, Zuin S, Wick P. Is nanotechnology revolutionizing the paint and lacquer industry? A critical opinion. Sci Total Environ. 2013;442:282–9.10.1016/j.scitotenv.2012.10.009Search in Google Scholar PubMed

[167] Kumar R, Nayak M, Sahoo GC, Pandey K, Sarkar MC, Ansari Y, et al. Iron oxide nanoparticles based antiviral activity of H1N1 influenza A virus. J Infect Chemother. 2019;25(5):325–9.10.1016/j.jiac.2018.12.006Search in Google Scholar PubMed

[168] Lin N, Verma D, Saini N, Arbi R, Munir M, Jovic M, et al. Antiviral nanoparticles for sanitizing surfaces: A roadmap to self-sterilizing against COVID-19. Nano Today. 2021;40:101267.10.1016/j.nantod.2021.101267Search in Google Scholar PubMed PubMed Central

[169] Wiehe A, O’Brien JM, Senge MO. Trends and targets in antiviral phototherapy. Photochem Photobiol Sci. 2019;18(11):2565–612.10.1039/c9pp00211aSearch in Google Scholar PubMed

[170] Ting D, Dong N, Fang L, Lu J, Bi J, Xiao S, et al. Multisite inhibitors for enteric coronavirus: Antiviral cationic carbon dots based on curcumin. ACS Appl Nano Mater. 2018;1(10):5451–9.10.1021/acsanm.8b00779Search in Google Scholar

[171] Milewska A, Kaminski K, Ciejka J, Kosowicz K, Zeglen S, Wojarski J, et al. HTCC: Broad range inhibitor of coronavirus entry. PLoS One. 2016;11(6):e0156552.10.1371/journal.pone.0156552Search in Google Scholar PubMed PubMed Central

[172] Smith RJ, Moule MG, Sule P, Smith T, Cirillo JD, Grunlan JC. Polyelectrolyte multilayer nanocoating dramatically reduces bacterial adhesion to polyester fabric. ACS Biomater Sci Eng. 2017;3(8):1845–52.10.1021/acsbiomaterials.7b00250Search in Google Scholar PubMed PubMed Central

[173] Ventura BD, Cennamo M, Minopoli A, Campanile R, Censi SB, Terracciano D, et al. Colorimetric test for fast detection of SARS-CoV-2 in nasal and throat swabs. ACS Sens. 2020;5(10):3043–8.10.1021/acssensors.0c01742Search in Google Scholar PubMed PubMed Central

[174] Hassanzadeh P. Nanotheranostics against COVID-19: From multivalent to immune-targeted materials. J. Controlled Release. 2020;328:112–26.10.1016/j.jconrel.2020.08.060Search in Google Scholar PubMed PubMed Central

[175] Huang C, Wen T, Shi F-J, Zeng X-Y, Jiao Y-J. Rapid detection of IgM antibodies against the SARS-CoV-2 virus via colloidal gold nanoparticle-based lateral-flow assay. ACS Omega. 2020;5(21):12550–6.10.1021/acsomega.0c01554Search in Google Scholar PubMed PubMed Central

[176] Li Z, Yi Y, Luo X, Xiong N, Liu Y, Li S, et al. Development and clinical application of a rapid IgM‐IgG combined antibody test for SARS‐CoV‐2 infection diagnosis. J Med Virol. 2020;92(9):1518–24.10.1002/jmv.25727Search in Google Scholar PubMed PubMed Central

[177] Baker AN, Richards S-J, Guy CS, Congdon TR, Hasan M, Zwetsloot AJ, et al. The SARS-COV-2 spike protein binds sialic acids and enables rapid detection in a lateral flow point of care diagnostic device. ACS Cent Sci. 2020;6(11):2046–52.10.1021/acscentsci.0c00855Search in Google Scholar PubMed PubMed Central

[178] Moitra P, Alafeef M, Dighe K, Frieman MB, Pan D. Selective naked-eye detection of SARS-CoV-2 mediated by N gene targeted antisense oligonucleotide capped plasmonic nanoparticles. ACS nano. 2020;14(6):7617–27.10.1021/acsnano.0c03822Search in Google Scholar PubMed PubMed Central

[179] Liu H, Dai E, Xiao R, Zhou Z, Zhang M, Bai Z, et al. Development of a SERS-based lateral flow immunoassay for rapid and ultra-sensitive detection of anti-SARS-CoV-2 IgM/IgG in clinical samples. Sens Actuators B. 2021;329:129196.10.1016/j.snb.2020.129196Search in Google Scholar PubMed PubMed Central

[180] Chen Z, Zhang Z, Zhai X, Li Y, Lin L, Zhao H, et al. Rapid and sensitive detection of anti-SARS-CoV-2 IgG, using lanthanide-doped nanoparticles-based lateral flow immunoassay. Anal Chem. 2020;92(10):7226–31.10.1021/acs.analchem.0c00784Search in Google Scholar PubMed PubMed Central

[181] Wang Z, Zheng Z, Hu H, Zhou Q, Liu W, Li X, et al. A point-of-care selenium nanoparticle-based test for the combined detection of anti-SARS-CoV-2 IgM and IgG in human serum and blood. Lab-on-a-Chip. 2020;20(22):4255–61.10.1039/D0LC00828ASearch in Google Scholar

[182] Wang D, He S, Wang X, Yan Y, Liu J, Wu S, et al. Rapid lateral flow immunoassay for the fluorescence detection of SARS-CoV-2 RNA. Nat Biomed Eng. 2020;4(12):1150–8.10.1038/s41551-020-00655-zSearch in Google Scholar PubMed

[183] Seo G, Lee G, Kim MJ, Baek S-H, Choi M, Ku KB, et al. Rapid detection of COVID-19 causative virus (SARS-CoV-2) in human nasopharyngeal swab specimens using field-effect transistor-based biosensor. ACS nano. 2020;14(4):5135–42.10.1021/acsnano.0c02823Search in Google Scholar PubMed PubMed Central

[184] Khoris IM, Ganganboina AB, Suzuki T, Park EY. Self-assembled chromogen-loaded polymeric cocoon for respiratory virus detection. Nanoscale. 2021;13(1):388–96.10.1039/D0NR06893DSearch in Google Scholar PubMed

[185] Yüce M, Filiztekin E, Özkaya KG. COVID-19 diagnosis—A review of current methods. Biosens Bioelectron. 2021;172:112752.10.1016/j.bios.2020.112752Search in Google Scholar PubMed PubMed Central

[186] Kyle S. Affimer proteins: Theranostics of the future? Trends Biochem Sci. 2018;43(4):230–2.10.1016/j.tibs.2018.03.001Search in Google Scholar PubMed

[187] Singh R, Hong S, Jang J. Label-free detection of influenza viruses using a reduced graphene oxide-based electrochemical immunosensor integrated with a microfluidic platform. Sci Rep. 2017;7(1):1–11.10.1038/srep42771Search in Google Scholar PubMed PubMed Central

[188] Qomara WF, Primanissa DN, Amalia SH, Purwadi FV, Zakiyah N. Effectiveness of remdesivir, lopinavir/ritonavir, and favipiravir for COVID-19 treatment: A systematic review. Int J Gen Med. 2021;14:8557.10.2147/IJGM.S332458Search in Google Scholar PubMed PubMed Central

[189] Fabra MJ, Falcó I, Randazzo W, Sánchez G, López-Rubio A. Antiviral and antioxidant properties of active alginate edible films containing phenolic extracts. Food Hydrocoll. 2018;81:96–103.10.1016/j.foodhyd.2018.02.026Search in Google Scholar

[190] Soria-Martinez L, Bauer S, Giesler M, Schelhaas S, Materlik J, Janus K, et al. Prophylactic antiviral activity of sulfated glycomimetic oligomers and polymers. J Am Chem Soc. 2020;142(11):5252–65.10.1021/jacs.9b13484Search in Google Scholar PubMed

[191] Günther SC, Maier JD, Vetter J, Podvalnyy N, Khanzhin N, Hennet T, et al. Antiviral potential of 3′-sialyllactose-and 6′-sialyllactose-conjugated dendritic polymers against human and avian influenza viruses. Sci Rep. 2020;10(1):1–9.10.1038/s41598-020-57608-4Search in Google Scholar PubMed PubMed Central

[192] Donskyi IS, Nie C, Ludwig K, Trimpert J, Ahmed R, Quaas E, et al. Graphene sheets with defined dual functionalities for the strong SARS‐CoV‐2 interactions. Small. 2021;17(11):2007091.10.1002/smll.202007091Search in Google Scholar PubMed PubMed Central

[193] Ramos-Soriano J, Reina JJ, Illescas BM, De La Cruz N, Rodriguez-Perez L, Lasala F, et al. Synthesis of highly efficient multivalent disaccharide/[60] fullerene nanoballs for emergent viruses. J Am Chem Soc. 2019;141(38):15403–12.10.1021/jacs.9b08003Search in Google Scholar PubMed

[194] Tong T, Hu H, Zhou J, Deng S, Zhang X, Tang W, et al. Glycyrrhizic‐acid‐based carbon dots with high antiviral activity by multisite inhibition mechanisms. Small. 2020;16(13):1906206.10.1002/smll.201906206Search in Google Scholar PubMed PubMed Central

[195] Kim H-E, Lee H-J, Kim MS, Kim T, Lee H, Kim H-H, et al. Differential microbicidal effects of bimetallic iron–copper nanoparticles on Escherichia coli and MS2 Coliphage. Environ Sci Technol. 2019;53(5):2679–87.10.1021/acs.est.8b06077Search in Google Scholar PubMed

[196] Kim J, Mukherjee A, Nelson D, Jozic A, Sahay G. Rapid generation of circulating and mucosal decoy ACE2 using mRNA nanotherapeutics for the potential treatment of SARS-CoV-2. BioRxiv. 2020.10.1002/advs.202202556Search in Google Scholar PubMed PubMed Central

[197] Wang C, Wang S, Chen Y, Zhao J, Han S, Zhao G, et al. Membrane nanoparticles derived from ACE2-rich cells block SARS-CoV-2 infection. ACS nano. 2021;15(4):6340–51.10.1021/acsnano.0c06836Search in Google Scholar PubMed PubMed Central

[198] Surnar B, Kamran MZ, Shah AS, Dhar S. Clinically approved antiviral drug in an orally administrable nanoparticle for COVID-19. ACS Pharmacol Transl Sci. 2020;3(6):1371–80.10.1021/acsptsci.0c00179Search in Google Scholar PubMed PubMed Central

[199] Zhang Q, Honko A, Zhou J, Gong H, Downs SN, Vasquez JH, et al. Cellular nanosponges inhibit SARS-CoV-2 infectivity. Nano Lett. 2020;20(7):5570–4.10.1021/acs.nanolett.0c02278Search in Google Scholar PubMed PubMed Central

[200] Morad R, Akbari M, Rezaee P, Koochaki A, Maaza M, Jamshidi Z. First principle simulation of coated hydroxychloroquine on Ag, Au and Pt nanoparticles. Sci Rep. 2021;11(1):1–9.10.1038/s41598-021-81617-6Search in Google Scholar PubMed PubMed Central

[201] Neufurth M, Wang X, Tolba E, Lieberwirth I, Wang S, Schröder HC, et al. The inorganic polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations. Biochem Pharmacol. 2020;182:114215.10.1016/j.bcp.2020.114215Search in Google Scholar PubMed PubMed Central

[202] Martínez-Abad A, Ocio M, Lagarón J, Sánchez G. Evaluation of silver-infused polylactide films for inactivation of Salmonella and feline calicivirus in vitro and on fresh-cut vegetables. Int J Food Microbiol. 2013;162(1):89–94.10.1016/j.ijfoodmicro.2012.12.024Search in Google Scholar PubMed

[203] Hu R, Li S, Kong F, Hou R, Guan X, Guo F. Inhibition effect of silver nanoparticles on herpes simplex virus 2. Genet Mol Res. 2014;13(3):7022–8.10.4238/2014.March.19.2Search in Google Scholar PubMed

[204] Park HH, Park S, Ko G, Woo K. Magnetic hybrid colloids decorated with Ag nanoparticles bite away bacteria and chemisorb viruses. J Mater Chem B. 2013;1(21):2701–9.10.1039/c3tb20311eSearch in Google Scholar PubMed

[205] Castro Mayorga JL, Fabra Rovira MJ, Cabedo Mas L, Sánchez Moragas G, Lagarón Cabello JM. Antimicrobial nanocomposites and electrospun coatings based on poly (3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) and copper oxide nanoparticles for active packaging and coating applications. J Appl Polym Sci. 2018;135(2):45673.10.1002/app.45673Search in Google Scholar

[206] Baram‐Pinto D, Shukla S, Gedanken A, Sarid R. Inhibition of HSV‐1 attachment, entry, and cell‐to‐cell spread by functionalized multivalent gold nanoparticles. Small. 2010;6(9):1044–50.10.1002/smll.200902384Search in Google Scholar PubMed

[207] Dunnill CW, Parkin IP. Nitrogen-doped TiO2thin films: Photocatalytic applications for healthcare environments. Dalton Trans. 2011;40(8):1635–40.10.1039/C0DT00494DSearch in Google Scholar PubMed

[208] Govorov AO, Richardson HH. Generating heat with metal nanoparticles. Nano Today. 2007;2(1):30–8.10.1016/S1748-0132(07)70017-8Search in Google Scholar

[209] Bogdan J, Zarzyńska J, Pławińska-Czarnak J. Comparison of infectious agents susceptibility to photocatalytic effects of nanosized titanium and zinc oxides: A practical approach. Nanoscale Res Lett. 2015;10(1):1–15.10.1186/s11671-015-1023-zSearch in Google Scholar PubMed PubMed Central

[210] Serrano-Aroca Á, Takayama K, Tuñón-Molina A, Seyran M, Hassan SS, Pal Choudhury P, et al. Carbon-based nanomaterials: Promising antiviral agents to combat COVID-19 in the microbial-resistant era. ACS nano. 2021;15(5):8069–86.10.1021/acsnano.1c00629Search in Google Scholar PubMed PubMed Central

[211] Sametband M, Kalt I, Gedanken A, Sarid R. Herpes simplex virus type-1 attachment inhibition by functionalized graphene oxide. ACS Appl Mater Interfaces. 2014;6(2):1228–35.10.1021/am405040zSearch in Google Scholar PubMed

[212] Ye S, Shao K, Li Z, Guo N, Zuo Y, Li Q, et al. Antiviral activity of graphene oxide: How sharp edged structure and charge matter. ACS Appl Mater Interfaces. 2015;7(38):21571–9.10.1021/acsami.5b06876Search in Google Scholar PubMed

[213] Gholami MF, Lauster D, Ludwig K, Storm J, Ziem B, Severin N, et al. Functionalized graphene as extracellular matrix mimics: Toward well‐defined 2D nanomaterials for multivalent virus interactions. Adv Funct Mater. 2017;27(15):1606477.10.1002/adfm.201606477Search in Google Scholar

[214] Vaillant A. Nucleic acid polymers: Broad spectrum antiviral activity, antiviral mechanisms and optimization for the treatment of hepatitis B and hepatitis D infection. Antivir Res. 2016;133:32–40.10.1016/j.antiviral.2016.07.004Search in Google Scholar PubMed

[215] Tengdelius M, Lee C-J, Grenegård M, Griffith M, Påhlsson P, Konradsson P. Synthesis and biological evaluation of fucoidan-mimetic glycopolymers through cyanoxyl-mediated free-radical polymerization. Biomacromolecules. 2014;15(7):2359–68.10.1021/bm5002312Search in Google Scholar PubMed

[216] Longarela OL, Schmidt TT, Schöneweis K, Romeo R, Wedemeyer H, Urban S, et al. Proteoglycans act as cellular hepatitis delta virus attachment receptors. PLoS One. 2013;8(3):e58340.10.1371/journal.pone.0058340Search in Google Scholar PubMed PubMed Central

[217] Richards KF, Bienkowska-Haba M, Dasgupta J, Chen XS, Sapp M. Multiple heparan sulfate binding site engagements are required for the infectious entry of human papillomavirus type 16. J Virol. 2013;87(21):11426–37.10.1128/JVI.01721-13Search in Google Scholar PubMed PubMed Central

[218] Cerqueira C, Liu Y, Kühling L, Chai W, Hafezi W, van Kuppevelt TH, et al. Heparin increases the infectivity of Human Papillomavirus Type 16 independent of cell surface proteoglycans and induces L1 epitope exposure. Cell Microbiol. 2013;15(11):1818–36.10.1111/cmi.12150Search in Google Scholar PubMed PubMed Central

[219] Dey P, Bergmann T, Cuellar-Camacho JL, Ehrmann S, Chowdhury MS, Zhang M, et al. Multivalent flexible nanogels exhibit broad-spectrum antiviral activity by blocking virus entry. ACS nano. 2018;12(7):6429–42.10.1021/acsnano.8b01616Search in Google Scholar PubMed

[220] Leibbrandt A, Meier C, König-Schuster M, Weinmüllner R, Kalthoff D, Pflugfelder B, et al. Iota-carrageenan is a potent inhibitor of influenza a virus infection. PLoS One. 2010;5(12):e14320.10.1371/journal.pone.0014320Search in Google Scholar PubMed PubMed Central

[221] Buck CB, Thompson CD, Roberts JN, Müller M, Lowy DR, Schiller JT. Carrageenan is a potent inhibitor of papillomavirus infection. PLoS Pathog. 2006;2(7):e69.10.1371/journal.ppat.0020069Search in Google Scholar PubMed PubMed Central

[222] Magnan S, Tota J, El-Zein M, Burchell A, Schiller J, Ferenczy A, et al. Efficacy of a carrageenan gel against transmission of cervical HPV (CATCH): Interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial. Clin Microbiol Infect. 2019;25(2):210–6.10.1016/j.cmi.2018.04.012Search in Google Scholar PubMed PubMed Central

[223] Zheng M, Qu D, Wang H, Sun Z, Liu X, Chen J, et al. Intranasal administration of chitosan against influenza A (H7N9) virus infection in a mouse model. Sci Rep. 2016;6:28729.10.1038/srep28729Search in Google Scholar PubMed PubMed Central

[224] Kyluik DL, Sutton TC, Le Y, Scott MD. Polymer-mediated broad spectrum antiviral prophylaxis: Utility in high risk environments. Progress in molecular and environmental bioengineering-from analysis and modeling to technology applications. Rijeka: Intech; 2011. p. 167–190.Search in Google Scholar

[225] Cai X, Prominski A, Lin Y, Ankenbruck N, Rosenberg J, Chen M, et al. A neutralizing antibody-conjugated photothermal nanoparticle captures and inactivates SARS-CoV-2. biorxiv. 2020. p. 11.10.1101/2020.11.30.404624Search in Google Scholar PubMed PubMed Central

[226] Roner MR, Carraher CE, Miller L, Mosca F, Slawek P, Haky JE, et al. Organotin Polymers as Antiviral Agents Including Inhibition of Zika and Vaccinia Viruses. J Inorg Organomet Polym Mater. 2020;30(3):684–94.10.1007/s10904-019-01250-9Search in Google Scholar

[227] Motiei M, Kashanian S, Lucia LA, Khazaei M. Intrinsic parameters for the synthesis and tuned properties of amphiphilic chitosan drug delivery nanocarriers. J Controlled Release. 2017;260:213–25.10.1016/j.jconrel.2017.06.010Search in Google Scholar PubMed

[228] Motiei M, Aboutalebi F, Forouzanfar M, Dormiani K, Nasr-Esfahani MH, Mirahmadi-Zare SZ. Smart co-delivery of miR-34a and cytotoxic peptides (LTX-315 and melittin) by chitosan based polyelectrolyte nanocarriers for specific cancer cell death induction. Mater Sci Eng C. 2021;128:112258.10.1016/j.msec.2021.112258Search in Google Scholar PubMed

[229] Nie C, Stadtmüller M, Yang H, Xia Y, Wolff T, Cheng C, et al. Spiky nanostructures with geometry-matching topography for virus inhibition. Nano Lett. 2020;20(7):5367–75.10.1021/acs.nanolett.0c01723Search in Google Scholar PubMed

[230] Hou YJ, Chiba S, Halfmann P, Ehre C, Kuroda M, Dinnon III KH, et al. SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo. Science. 2020;370(6523):1464–8.10.1126/science.abe8499Search in Google Scholar PubMed PubMed Central

[231] Purohit R, Mittal A, Dalela S, Warudkar V, Purohit K, Purohit S. Social, environmental and ethical impacts of nanotechnology. Mater Today Proc. 2017;4(4):5461–7.10.1016/j.matpr.2017.05.058Search in Google Scholar

[232] Weston S, Coleman CM, Haupt R, Logue J, Matthews K, Li Y, et al. Broad anti-coronavirus activity of food and drug administration-approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo. J Virol. 2020;94(21):e01218–20.10.1128/JVI.01218-20Search in Google Scholar PubMed PubMed Central

[233] Tharayil A, Rajakumari R, Chirayil CJ, Thomas S, Kalarikkal N A short review on nanotechnology interventions against COVID-19. Emergent Mater. 2021;4(1):131–41.10.1007/s42247-021-00163-zSearch in Google Scholar PubMed PubMed Central

Received: 2022-10-11

Revised: 2022-12-08

Accepted: 2023-01-16

Published Online: 2023-02-13

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

https://doi.org/10.1515/ntrev-2022-0515

Keywords for this article

viral pandemics; nanotechnology; prevention; diagnosis; treatment

Creative Commons

BY 4.0