Startseite Computational studies by molecular docking of some antiviral drugs with COVID-19 receptors are an approach to medication for COVID-19
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Computational studies by molecular docking of some antiviral drugs with COVID-19 receptors are an approach to medication for COVID-19

  • Magda H. Abdellatiif EMAIL logo , Amena Ali , Abuzer Ali und Mostafa A. Hussien
Veröffentlicht/Copyright: 3. März 2021
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Open Chemistry
Aus der Zeitschrift Open Chemistry Band 19 Heft 1

Abstract

The COVID-19 outbreak is a matter of concern worldwide due to unavailability of promising treatment comprising medication or vaccination till date. The discovery of antiviral drug is of immense importance in the existing spread of novel coronavirus. The goal of the present study was to evolve an opposite antiviral drug against the novel COVID-19 virus. A directly succeeding perspective would be to use the prevailing influential drugs from several antimicrobial and chemotherapeutic agents. The encouraging approach is to identify promising drug molecules and compounds through virtual screening via molecular docking of FDA-approved drugs and some previously synthesized pyridone and coumarin derivatives for probable therapeutic outcome. In this conceptual milieu, an effort has been made to propose a computational in silico relationship among FDA-approved drugs and coronavirus-associated receptors and proteins. The study results were evaluated on the basis of a dock score by using molecular operating environment. Out of 15 compounds screened, the compounds with the best docking scores toward their targets was 3d. Therefore, compound 3d deserves further investigations and clinical trials as a possible therapeutic inhibitor of the COVID-19 caused by the novel SARS-CoV-2.

Keywords: MOE; molecular docking; COVID-19; pyridones ; coumarin

Abbreviations

Binding score energy

It is the energy released when a drug molecule accompanied by a target, resulting in a lowering of the overall energy of the complex

Docking score

It is a procedure to quantify the predictive capability of a docking protocol. While scoring functions are mathematical functions which used to approximately predict the binding affinity between two molecules after they have been docked

PDB

protein data bank

MOE

Molecular operating environment

1 Introduction

Docking process includes both of prediction of ligand conformation and of orientation which means posing within a targeted binding site. The docking studies have two important aims, namely, are accurate structural modeling and correct prediction of activity. Mankind has formerly witnessed the outburst of numerous deadly pathogens such as Zika, Ebola, the Middle East respiratory syndrome (MERS) coronavirus, severe acute respiratory syndrome (SARS) coronavirus, and, currently, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1,2,3,4,5]. The novel COVID-19 pandemic is an ongoing global concern which is also known as the severe acute respiratory syndrome coronavirus spread worldwide [6,7]. The COVID-19 is extremely contagious and potentially fatal disease that can cause mild to severe respiratory tract infections. The COVID-19 outbreak has caused economic and social disruptions globally [8,9]. The contagious nature of COVID-19 infection led to the isolation of patients who were subsequently given various treatments [10,11,12]. The most problematic factor of the pandemic is the rate of transmission. Consequently, the numbers of patients are increasing day by day still with no treatment [13]. Undoubtedly, developing a new drug or vaccine typically takes a long time as it should be intensively tested and ensured to be safe through clinical trials prior to approval for human subjects [14,15]. Although many antiviral drugs and vaccines are undergoing clinical trials against COVID-19, none of them proved their safety and efficacy [16,17]. Currently the COVID-19 is a global pandemic and the situation is not under control [18]. Numerous scientists and researchers are working worldwide to find an efficient means to prevent the pandemic. Due to the unavailability of any approved antiviral drug for COVID-19 treatment, one of the best and fast way to find the antagonist of COVID-19 is through clinically screening the currently available drugs. Hence, repurposing of the clinically available drugs and the available antimicrobials in literature seems to be a faster way to get the target drug [19].

It is the matter of fact that the antimicrobial approach towards the prevention of pandemic could be very effective whereas coumarins and pyridones are effectively proved as antimicrobials [20,21,22,23]. However, some of them also exhibited antitumor, anticancer, analgesic, anti-HIV, antitubercular, and antiviral properties [24,25,26,27,28,29,30].

2-pyridone compounds were also shown to be potent nonnucleoside HBV inhibitors [31]. Coumarin is a natural compound and is a potential drug candidate owing to its properties of stability, solubility, and low toxicity. There are numerous evidences showing its inhibitory role against infection of various viruses such as HIV, influenza, enterovirus 71, and coxsackievirus A16 [32,33,34,35].

Virtual screening is a prevalent modeling tool broadly employed in structure-based drug design [36,37,38,39,40]. It is an imperative means to predict the binding affinity, type of interaction, and the suitable receptor-binding sites among the drug and corresponding receptor by using, for example, scoring functions. In the rational drug design and explicate fundamental biochemical processes, elucidating the binding behavior has an important role [41,42]. In the present study, molecular docking was performed on previously synthesized compounds and drugs mentioned in the clinical protocol of WHO for the treatment of COVID-19. The molecular operating environment (MOE) 2018 modeling program was utilized to predict the binding sites and docking score.

2 Methodology

2.1 Molecular docking method

All docking studies were performed using the MOE program 2018. Structure optimization of the compounds and all drugs that were used as inhibitor agents to COVID-19 was performed by Gaussian 09 program package [45] using the density functional theory with B3LYP [46] and the 6-311++G(d,p) basis sets. The crystal structure of target protein was retrieved from the Protein Data Bank (http://www.rcsb.org/pdb/). The Docking score in MOE software was utilizing and accompanied by the five poses for output refinement for final binding poses. Root-mean-square deviation (RMSD) of the compound position compared to the docking, the pose was used in ranking. Both RMSD and the mode of interaction of the native ligand within the structure of the receptor were used as the standard docked model [47,48,49,50,51,52,53]. Coronavirus has glycoprotein spikes arranged like a crown. Coronavirus infects its host in three stages. The first stage involves the virus infecting its host by attaching the transmembrane spike-conjugated protein to host through angiotensin-converting protein 2 (ACE 2) within the host so a fancy is formed between S-glycoprotein with ACE-2 with the assistance of transmembrane protease, aminoalkanoic acid 2 (TMPRSS2), produced by host cells. The consequent stage is the replication stage wherein the ribonucleic acid-dependent RNA polymerase (RdRp) is exploited. Coronaviruses are ribonucleic acid viruses that use host cells to replicate. Coronavirus uses RdRp to form new ribonucleic acid copies. The last stage is the maturation stage of virus replication within the host cell by exploiting proteases akin to 3C-like protease (3CLpro) and papain-like protease (PLpro). Some medication is proverbial to be able to inhibit these three processes as well as Arbidol as ACE2 inhibitors, camostat mesylate as TMPRSS2 inhibitors, remdesivir and antiviral agent as RdRp inhibitors, and lopinavir and protease inhibitor as protease inhibitors. Chloroquine, lopinavir, protease inhibitor, and remdesivir are antimicrobials that contain a potential activity against SARS-CoV 2. The target proteins, which are the targets of inhibition, are ACE2, TMPRSS 2, RdRP, 3CLpro, and PLpro [54,55,56,57].

  1. Ethical approval: The conducted research is not related to either human or animal use.

3 Result and discussion

In silico methods and computational molecular docking studies are effective tools, which are broadly utilized to interpret the molecular aspects of ligand–protein interactions during drug discovery against various prior fatal and emerging diseases including SARS coronavirus [41,42]. In the present study, the virtual screening of numerous previously synthesized 2-pyridone derivatives (1a–e) and acetyl coumarin derivatives (2a–e, 3a–e) [43,44], which were already reported to have anticancer and antibacterial activities along with the drugs used in WHO COVID-19 treatment protocol, was performed against the human angiotensin-converting enzyme (PDB code = 1O86), SARS-CoV-main peptidase (PDB code = 2GTB), serine protease hepsin (PDB code = 5CE1), human coronavirus papain-like proteases (PDB code = 4OW0), and SARS-Coronavirus NSP12 (PDB code = 6NUR) to discover the most predicated drug–ligand interactions. The obtained parameters contain the docking scores, binding efficiency of ligand, and hydrogen bonding interactions. The results of the molecular docking studies of pyridone and coumarin series against the aforementioned proteins were compared with that obtained using different drugs mentioned in the WHO’s clinical protocol of COVID-19 treatment such as Umifenovir, chloroquine, camostat, remdesivir, ribavirin, and lopinavir. The topmost compounds were carefully chosen and are presented in Tables 1–6 and Figures 1–5. The study results of the binding score energy of pyridone series represented in Table 2 for compounds 1a–e are −6.37, −6.54, −6.68, −7.03, and −6.21, respectively. By comparing these scores, one can find that compound 1d has higher binding score energy than ribavirin and it is near to the binding score energy values of chloroquine. Also compounds 1a–c are most active compared to ribavirin while this series is of less activity toward 1O86 as compared to references Umifenovir, chloroquine, camostat, remdesivir, and lopinavir. This means only compound 1d is the most welcome compound in this series toward 1O86.

Table 1

Interaction table between the compounds and the chosen standard antiviral with 1O86 protein

Compound no. Ligand Receptor Interaction Distance E (kcal/mol)
1a N 21 NZ LYS 368 (A) H-acceptor 3.52 −0.9
1b N 21 NE2 GLN 281 (A) H-acceptor 3.30 −0.8
1c No measurable interaction
1d O 20 NH1 ARG 124 (A) H-acceptor 2.86 −3.8
1e No measurable interaction
2a O 16 ND2 ASN 66 (A) H-acceptor 3.08 −0.6
O 20 ND2 ASN 70 (A) H-acceptor 3.05 −0.6
6-Ring ND2 ASN 66 (A) pi-H 4.29 −1.9
2b 5-Ring 5-Ring HIS 387 (A) pi–pi 3.67 −0.0
3a O 16 ND2 ASN 66 (A) H-acceptor 2.97 −0.9
6-Ring ND2 ASN 66 (A) pi-H 4.24 −1.1
6-Ring ND2 ASN 70 (A) pi-H 4.04 −0.6
3b 5-Ring 6-Ring TRP 357 (A) pi–pi 3.87 −0.0
2c Cl 33 O ALA 356 (A) H-donor 3.11 −1.0
2d 6-Ring CA TRP 357 (A) pi-H 4.67 −0.6
2e O 16 N GLY 404 (A) H-acceptor 2.90 −0.7
6-Ring CB GLU 403 (A) pi-H 3.64 −0.7
3c N 20 N ALA 354 (A) H-acceptor 3.56 −1.2
3d No measurable interaction
3e O 39 ND2 ASN 70 (A) H-acceptor 2.96 −0.9
O 40 ND2 ASN 66 (A) H-acceptor 3.22 −0.9
6-Ring CB SER 516 (A) pi-H 4.63 −0.5
Umifenovir 6-Ring CE LYS 118 (A) pi-H 4.24 −0.6
Chloroquine No measurable interaction
Camostat N 46 OD2 ASP 121 (A) H-donor 3.02 −0.7
Remdesivir N 18 O ALA 356 (A) H-donor 3.28 −1.7
N 64 O GLY 404 (A) H-donor 3.02 −1.9
O 15 N ALA 356 (A) H-acceptor 3.03 −1.7
O 46 NH1 ARG 522 (A) H-acceptor 3.04 −2.4
O 48 NH2 ARG 522 (A) H-acceptor 3.05 −2.6
C 8 5-Ring TRP 357 (A) H-pi 4.02 −1.0
6-Ring CB GLU 403 (A) pi-H 3.61 −0.6
6-Ring CG PRO 407 (A) pi-H 3.63 −1.2
5-Ring CG PRO 407 (A) pi-H 4.30 −1.0
Ribavirin 5-Ring NE1 TRP 220 (A) pi-H 3.56 −0.5
Lopinavir No measurable interaction
Table 2

Docking score and energy of the compounds and 1O86 protein

Compound no. S rmsd_refine E_conf E_place E_score1 E_refine E_score2
1a −6.37 1.02 −16.27 −66.62 −10.02 −31.98 −6.37
1b −6.54 2.50 −23.65 −81.96 −8.78 −30.27 −6.54
1c −6.68 1.14 12.36 −75.69 −8.37 −33.36 −6.68
1d −7.03 1.43 4.52 −76.10 −8.26 −26.88 −7.03
1e −6.21 2.92 −27.41 −73.64 −8.72 −29.02 −6.21
2a −6.21 1.15 23.41 −68.11 −8.85 −25.31 −6.21
2b −6.35 1.08 20.40 −59.03 −7.31 −27.76 −6.35
3a −6.08 1.65 −5.45 −57.69 −9.35 −21.97 −6.08
3b −6.48 1.94 −35.75 −61.15 −8.42 −27.07 −6.48
2c −6.69 2.16 5.42 −60.47 −8.09 −25.61 −6.69
2d −6.84 0.87 1.60 −62.11 −8.53 −33.04 −6.84
2e −6.63 1.74 29.04 −71.02 −7.79 −36.82 −6.63
3c −6.78 1.34 −45.58 −69.60 −9.10 −32.78 −6.78
3d −7.08 0.59 −48.41 −70.78 −8.50 −30.15 −7.08
3e −6.63 1.24 −36.97 −64.11 −8.07 −33.60 −6.63
Compound no. S rmsd_refine E_conf E_place E_score1 E_refine E_score2
Umifenovir −7.26 1.33 65.41 −93.92 −10.48 −41.11 −7.26
Chloroquine −7.10 1.64 −45.50 −65.54 −9.39 −37.52 −7.10
Camostat −7.71 1.80 −116.94 −78.17 −9.95 −34.14 −7.71
Remdesivir −9.21 1.59 −29.39 −114.79 −9.90 −56.98 −9.21
Ribavirin −6.17 1.16 149.11 −71.88 −11.60 −24.89 −6.17
Lopinavir −9.19 2.47 −59.70 −51.38 −9.40 −54.28 −9.19
Table 3

Interaction table between the compounds and the chosen standard antiviral with 2GTB protein

Ligand Receptor Interaction Distance E (kcal/mol)
1a O 34 SG CYS 44 (A) H-donor 3.32 −2.4
N 21 N GLY 143 (A) H-acceptor 3.12 −0.7
N 21 OG SER 144 (A) H-acceptor 3.03 −1.3
N 21 N CYS 145 (A) H-acceptor 3.45 −0.6
1b C 24 SG CYS 44 (A) H-donor 4.30 −0.5
O 33 SD MET 165 (A) H-donor 3.57 −1.0
6-Ring NE2 GLN 189 (A) pi-H 4.31 −0.6
6-Ring 5-Ring HIS 41 (A) pi–pi 3.84 −0.0
1c N 21 NE2 HIS 163 (A) H-acceptor 3.19 −4.3
1d 6-Ring NE2 GLN 189 (A) pi-H 3.80 −1.3
1e O 20 SG CYS 44 (A) H-donor 3.62 −1.5
N 33 OE2 GLU 166 (A) H-donor 2.99 −1.3
O 32 NE2 HIS 163 (A) H-acceptor 3.19 −3.4
6-Ring 5-Ring HIS 41 (A) pi–pi 3.95 −0.0
2a 6-Ring NE2 GLN 189 (A) pi-H 3.67 −2.8
2b 5-Ring NE2 GLN 189 (A) pi-H 4.04 −0.5
5-Ring 5-Ring HIS 41 (A) pi–pi 3.81 −0.0
3a N 20 N GLY 143 (A) H-acceptor 3.24 −3.4
6-Ring NE2 GLN 189 (A) pi-H 3.71 −4.4
3b C 9 SG CYS 44 (A) H-donor 3.61 −0.6
S 31 SG CYS 145 (A) H-donor 4.38 −1.0
N 20 N GLY 143 (A) H-acceptor 3.04 −4.4
6-Ring NE2 GLN 189 (A) pi-H 4.29 −0.7
6-Ring 5-Ring HIS 41 (A) pi–pi 3.93 −0.0
2d C 9 SG CYS 44 (A) H-donor 3.64 −0.7
2e O 20 N GLY 143 (A) H-acceptor 3.18 −2.6
2e C 21 SD MET 165 (A) H-donor 3.94 −0.5
O 20 N GLU 166 (A) H-acceptor 3.29 −1.1
3c N 18 N GLY 143 (A) H-acceptor 3.57 −1.2
6-Ring NE2 GLN 189 (A) pi-H 4.08 −1.5
6-Ring 5-Ring HIS 41 (A) pi–pi 3.80 −0.0
3d N 18 N GLY 143 (A) H-acceptor 3.30 −2.8
3e N 20 N GLY 143 (A) H-acceptor 3.34 −2.7
6-Ring NE2 GLN 189 (A) pi-H 3.71 −2.3
Umifenovir O 10 N GLY 143 (A) H-acceptor 2.91 −3.6
Chloroquine No measurable interactions
Camostat N 46 OE1 GLU 166 (A) H-donor 3.05 −3.1
N 46 OE2 GLU 166 (A) H-donor 3.45 −0.6
O 33 NE2 HIS 163 (A) H-acceptor 2.83 −0.6
N 46 OE1 GLU 166 (A) H-donor 3.05 −3.1
N 46 OE2 GLU 166 (A) H-donor 3.45 −0.6
O 33 NE2 HIS 163 (A) H-acceptor 2.83 −0.6
Remdesivir O 46 N GLU 166 (A) H-acceptor 3.11 −2.0
N 51 N GLY 143 (A) H-acceptor 3.15 −0.5
N 51 OG SER 144 (A) H-acceptor 2.98 −1.4
N 51 N CYS 145 (A) H-acceptor 3.48 −0.5
6-Ring 5-Ring HIS 41 (A) pi–pi 3.94 −0.0
Ribavirin O 1 NE2 HIS 163 (A) H-acceptor 3.05 −1.8
O 11 N GLY 143 (A) H-acceptor 2.95 −1.0
Lopinavir 6-Ring CG2 THR 25 (A) pi-H 3.51 −0.5
6-Ring NE2 GLN 189 (A) pi-H 4.16 −0.6
Table 4

Docking score and energy of the compounds and 2GTB protein

Compound no. S rmsd_refine E_conf E_place E_score1 E_refine E_score2
1a −6.39 0.86 −15.41 −93.48 −12.13 −35.80 −6.39
1b −6.23 4.35 −27.56 −85.95 −10.81 −27.15 −6.23
1c −7.21 1.05 13.71 −79.21 −10.20 −39.41 −7.21
1d −6.98 0.98 3.69 −91.33 −10.55 −35.61 −6.98
1e −6.64 2.15 −26.64 −73.15 −10.30 −37.62 −6.64
2a −6.16 0.79 24.13 −63.97 −9.83 −31.93 −6.16
2b −6.16 1.79 17.64 −67.10 −9.47 −33.34 −6.16
3a −6.72 0.75 −10.66 −67.50 −10.24 −36.42 −6.72
3b −6.67 1.34 −31.64 −72.99 −9.69 −36.68 −6.67
2c −6.29 2.66 6.07 −55.90 −9.17 −31.41 −6.29
2d −7.17 1.49 6.40 −63.99 −9.16 −35.81 −7.17
2e −6.78 1.28 32.80 −55.31 −10.23 −35.19 −6.78
3c −6.85 1.19 −47.33 −84.62 −11.09 −37.93 −6.85
3d −7.62 2.04 −43.55 −71.67 −9.51 −39.18 −7.62
3e −7.45 2.23 −35.30 −56.56 −11.05 −38.79 −7.45
Compound no. S S E_conf E_place E_score1 E_refine E_score2
Umifenovir −7.23 2.36 72.87 −63.18 −10.11 −37.59 −7.23
Chloroquine −7.03 1.69 −26.96 −52.10 −9.48 −32.28 −7.03
Camostat −7.37 1.90 −121.50 −62.62 −9.67 −42.81 −7.37
Remdesivir −8.64 1.39 −43.66 −89.43 −9.74 −47.34 −8.64
Ribavirin −5.59 1.28 154.07 −75.52 −9.82 −25.79 −5.59
Lopinavir −8.66 1.81 −60.54 −53.88 −8.62 −50.98 −8.66
Table 5

Interaction table between the compounds and the chosen standard antiviral with 4OW0 protein

Ligand Receptor Interaction Distance E (kcal/mol)
1a O 34 O GLN 270 (A) H-donor 3.05 −1.1
1b N 34 O TYR 269 (A) H-donor 3.01 −3.2
N 34 6-Ring TYR 269 (A) H-pi 3.68 −1.0
1c No measurable interactions
1d O 20 NE2 GLN 233 (B) H-acceptor 3.00 −0.6
1e N 33 O TYR 269 (A) H-donor 3.12 −2.1
N 3 5-Ring HIS 172 (A) H-pi 4.53 −2.1
6-Ring OH TYR 269 (A) pi-H 4.45 −0.5
2a 5-Ring CD LYS 158 (A) pi-H 3.68 −1.6
2b 5-Ring CD LYS 158 (A) pi-H 3.65 −0.5
3a 6-Ring NZ LYS 158 (A) pi-cation 4.35 −0.6
3b No measurable interactions
2c O 20 N MET 209 (B) H-acceptor 3.05 −1.3
6-Ring CG GLU 162 (A) pi-H 3.55 −0.6
2d O 20 NH1 ARG 167 (B) H-acceptor 3.13 −1.6
6-Ring NZ LYS 158 (A) pi-cation 4.26 −0.5
6-Ring NZ LYS 158 (A) pi-cation 3.94 −8.2
6-Ring N MET 209 (B) pi-H 3.89 −0.6
2e O 35 N ASP 165 (A) H-acceptor 2.98 −1.0
3c 6-Ring 6-Ring TYR 265 (A) pi–pi 3.89 −0.0
3d N 18 NH1 ARG 167 (B) H-acceptor 3.53 −0.6
6-Ring NZ LYS 158 (A) pi-cation 3.75 −7.3
3e 6-Ring NZ LYS 158 (A) pi-cation 4.55 −0.8
6-Ring CB LEU 163 (A) pi-H 4.35 −0.8
Umifenovir No measurable interactions
Chloroquine 6-Ring N MET 209 (B) pi-H 3.84 −1.0
6-Ring CB MET 209 (B) pi-H 4.55 −0.5
Camostat N 49 OG1 THR 302 (A) H-donor 2.90 −1.8
Remdesivir N 18 O MET 209 (B) H-donor 3.13 −2.7
N 64 O ASP 165 (A) H-donor 3.43 −1.1
O 21 NZ LYS 158 (A) H-acceptor 3.15 −2.5
5-Ring NZ LYS 158 (A) pi-cation 3.94 −0.6
6-Ring CD LYS 158 (A) pi-H 3.51 −0.7
Ribavirin O 1 O ASN 157 (A) H-donor 3.08 −0.7
N 23 O MET 209 (B) H-donor 2.98 −1.8
O 11 NH1 ARG 167 (B) H-acceptor 2.98 −1.8
5-Ring CA TYR 208 (B) pi-H 3.80 −1.1
Lopinavir N 30 O LEU 163 (A) H-donor 3.33 −1.1
Table 6

Interaction table between the compounds and the chosen standard antiviral with 4OW0 protein

Compound no. S rmsd_refine E_conf E_place E_score1 E_refine E_score2
1a −6.60 1.04 −14.69 −90.64 −10.33 −37.54 −6.60
1b −7.50 0.56 4.93 −89.24 −12.71 −44.58 −7.50
1c −7.39 1.59 15.44 −71.87 −11.23 −38.11 −7.39
1d −7.55 1.13 4.90 −87.71 −10.99 −38.90 −7.55
1e −6.99 2.73 −26.09 −99.80 −10.51 −37.12 −6.99
2a −6.81 3.16 25.82 −73.59 −9.34 −33.99 −6.81
2b −6.96 2.03 17.99 −78.37 −10.07 −36.24 −6.96
3a −7.43 2.55 −11.31 −70.99 −9.87 −37.37 −7.43
3b −7.34 1.02 −30.37 −70.77 −10.21 −34.92 −7.34
2c −6.76 1.02 0.91 −84.15 −9.92 −37.08 −6.76
2d −7.45 1.87 2.22 −71.40 −10.62 −37.53 −7.45
2e −7.12 1.85 32.33 −79.24 −10.77 −38.91 −7.12
3c −7.34 1.09 −45.36 −79.77 −10.46 −36.84 −7.34
3d −8.22 1.19 −45.54 −72.67 −11.35 −38.56 −8.22
3e −7.34 1.14 −32.54 −72.93 −11.38 −37.08 −7.34
Compound no. S rmsd_refine E_conf E_place E_score1 E_refine E_score2
Umifenovir −8.31 3.61 66.94 −93.12 −10.71 −51.37 −8.31
Chloroquine −7.83 2.09 −44.03 −59.46 −9.80 −40.10 −7.83
Camostat −8.43 1.71 −120.22 −80.50 −10.85 −41.53 −8.43
Remdesivir −11.05 2.02 −34.05 −90.49 −10.39 −63.67 −11.05
Ribavirin −6.14 1.95 150.94 −87.71 −10.41 −29.69 −6.14
Lopinavir −11.50 2.00 −38.70 −104.83 −10.82 −61.13 −11.50
Figure 1 Pyridone series, which are docked by MOE and compared with different antiviral drugs [43].
Figure 1

Pyridone series, which are docked by MOE and compared with different antiviral drugs [43].

Figure 2 Coumarin compounds 2a–e and 3a–e, which are docked by MOE and compared with different antiviral drugs [44].
Figure 2

Coumarin compounds 2a–e and 3a–e, which are docked by MOE and compared with different antiviral drugs [44].

The same series was investigated for 2GTB protein, and the binding score energy is represented in Table 4. Compounds 1a–e showed the binding score energy −6.39, −6.23, −7.21, −6.98, and −6.64, respectively, and this series exhibited higher activity than ribavirin. Compound 1c represented a good activity near the binding score energy value of Umifenovir and camostat values, and higher than chloroquine binding score energy values. By examination of this series for 4OW0 in Table 6, it is noticed that they are more active than ribavirin only.

The study results of the binding score energy of 5CE1 protein shown in Table 8 indicated that the series is more active than ribavirin; while the binding score energy values of compounds 1c, 1d are near to camostat and Umifenovir values. The study results of this series for 6NUR protein is shown in Table 10, demonstrating higher binding score energy values than Umifenovir, chloroquine, and ribavirin.

The interaction between the compounds and the chosen standard antiviral with 1O86 protein is presented in Table 1. Compound 1a is bonded to Lys 368 by H-acceptor, compound 1b with GLN281 also by H-acceptor, and compound 1d is bonded to ARG 124 by H-acceptor; while compounds 1c and 1e as well chloroquine and lopinavir showed no measurable interaction with 1O86 protein.

Similarly, the interaction between the compounds and the chosen standard antivirals with 2GTB protein is given in Table 3, showing that compound 1a bonded to the receptors at Gly143 like Umifenovir, remdesivir, and ribavirin. While chloroquine has no measurable interaction. The interaction between the investigated compounds and the chosen standard antiviral with 4OW0 protein in Table 5 revealed that 1b is bonded with the receptor at GLN at 270(A), TYR 269(A), by H-donor, and TYR 269(A) with pi-interaction, while 1d is bonded to the receptor by H-acceptor at GLN233(B), 1e has interactions by H-donor, H-pi, and pi-H at receptor Tyr269(A), 5ring(His172(A), and OH-Tyr269(A), and no similarity was observed in the binding to the receptor like the references antiviral.

The interactions between the compounds and the chosen standard antiviral with 5CE1 protein is illustrated in Table 7. The receptor interacted with the ribavirin at GLY 380(A), and the results showed that compounds 1a, 1b, and 1d are bonded to the receptor from the same position and all of them are connected by H-acceptor. Compound 1b is bonded to the receptor at CYS 381(A), by H-donor like ribavirin and camostat, while compounds 1a, 1b, and 1c are bonded to the receptor by pi-H at position CYS 349(A) like chloroquine, remdesivir, and lopinavir.

Table 7

Interaction table between the compounds and the chosen standard antiviral with 5CE1 protein

Ligand Receptor Interaction Distance E (kcal/mol)
1a N 3 O GLY 380 (A) H-donor 2.82 −3.8
6-Ring CA CYS 349 (A) pi-H 4.09 −1.4
1b N 3 O GLY 380 (A) H-donor 2.79 −2.4
N 3 SG CYS 381 (A) H-donor 3.35 −0.5
N 9 N GLY 378 (A) H-acceptor 3.45 −0.5
6-Ring CA CYS 349 (A) pi-H 4.35 −0.6
1c N 3 O GLY 380 (A) H-donor 2.82 −4.2
6-Ring CA CYS 349 (A) pi-H 4.12 −0.8
6-Ring CG GLN 350 (A) pi-H 3.76 −0.5
1d N 3 O GLY 380 (A) H-donor 2.84 −3.1
1e 6-Ring CB GLN 350 (A) pi-H 4.21 −1.0
2a 6-Ring CA CYS 349 (A) pi-H 4.18 −0.9
5-Ring 5-Ring HIS 203 (A) pi–pi 3.53 −0.0
2b 6-Ring CA CYS 349 (A) pi-H 4.25 −0.6
3a 6-Ring CA CYS 349 (A) pi-H 4.19 −0.9
5-Ring 5-Ring HIS 203 (A) pi–pi 3.58 −0.0
3b 6-Ring CA CYS 349 (A) pi-H 4.23 −0.7
5-Ring 5-Ring HIS 203 (A) pi–pi 3.66 −0.0
2c 6-Ring CA CYS 349 (A) pi-H 4.12 −1.7
2d C 11 SG CYS 381 (A) H-donor 4.00 −0.5
2e 6-Ring CA CYS 349 (A) pi-H 4.23 −0.6
6-Ring CG GLN 350 (A) pi-H 4.18 −0.5
3c 6-Ring CA CYS 349 (A) pi-H 4.23 −0.7
6-Ring 5-Ring HIS 203 (A) pi–pi 3.99 −0.0
3d C 9 SG CYS 188 (A) H-donor 3.77 −0.5
O 16 N GLY 351 (A) H-acceptor 3.05 −2.7
3e No measurable interactions
Umifenovir O 10 OH TYR 301 (A) H-acceptor 3.05 −2.3
Chloroquine N 17 OG SER 353 (A) H-donor 3.06 −0.7
C 31 5-Ring HIS 203 (A) H-pi 4.06 −1.3
6-Ring CA CYS 349 (A) pi-H 4.25 −0.9
Camostat N 49 OD1 ASP 347 (A) H-donor 3.18 −1.9
Remdesivir O 21 SG CYS 381 (A) H-donor 3.72 −0.8
N 64 O CYS 204 (A) H-donor 3.07 −1.3
6-Ring CA CYS 349 (A) pi-H 4.23 −0.9
Ribavirin O 1 O GLY 380 (A) H-donor 2.97 −0.6
N 23 OD2 ASP 347 (A) H-donor 3.13 −3.0
N 23 SG CYS 381 (A) H-donor 4.37 −1.1
Lopinavir C 74 OE2 GLU 252 (A) H-donor 3.25 −0.5
O 33 OG SER 353 (A) H-acceptor 2.82 −2.2
6-Ring CA CYS 349 (A) pi-H 4.25 −0.6
6-Ring CA THR 379 (A) pi-H 4.45 −0.9

The interactions between the compounds and the chosen standard antiviral with 6NUR protein are represented in Table 9. As a whole, compound 1c has no measurable interaction. Compounds 1a and 1b are bonded to the receptor from ARG 624(A), by H-acceptor like Umifenovir, chloroquine, ribavirin, and lopinavir.

Compounds 1a, 1b, and 1d represented interactions with the receptor at ARG 555(A), like lopinavir although they are interacted by H-donor, and lopinavir is bonded by pi-cation to the receptor. Compound 1a interacts with the receptor at SER 682(A), by pi-H like remdesivir, while camostat is bonded to the same position but by H-acceptor interaction. Camostat is also bonded to the receptor at ARG 553 by pi-H while Umifenovir is bonded by pi-cation, and compound 1b is bonded to the same receptor, but compounds 1d and 1e are bonded by H-acceptor.

The study results of the coumarin series for 1O86 protein and the binding score energy are represented in Table 2. From the data obtained in Table 1, it is observed that compounds 2a, 2b, 2c, 2d, and 2e have binding score energy values of −6.21, −6.35, −6.69, −6.84, and −6.63, respectively. It is clear that all of them have higher docking score than ribavirin. Compounds 3a, 3b, 3c, 3d, and 3e have binding score energy values of −6.08, −6.48, −6.78, −7.08, and −6.63 respectively, and it is noticed that all of them have higher docking score than ribavirin while only compound 3d’s score was near chloroquine. Hence, it is concluded that compound 3d is the most welcomed compound in this series for 1O86.

The same series was examined for 2GTB protein and the binding score energy is represented in Table 4. Compounds 2a, 2b, 2c, 2d, and, 2e have binding score energy values of −6.16, −6.16, −6.29, −7.17, and −6.78 respectively, and it is apparent that all of them scored higher than ribavirin. While compound 2d has binding score energy values higher than chloroquine. While compounds 3a, 3b, 3c, 3d, and 3e have binding score energy values of −6.72, −6.67, −6.85, −7.62, and −7.45, respectively. It is revealed that all of them have higher binding score than ribavirin. Furthermore, compounds 3d and 3e have binding score energy values higher than Umifenovir, camostat, and chloroquine. This means that compound 3d is the most active one toward 2GTB protein.

The results of the binding score energy of the same series for 4OW0 protein are represented in Table 6. Compounds 2a, 2b, 2c, 2d, and 2e have −6.81, −6.96, −6.76, −7.45, and −7.12 respectively, and all of them scored higher than ribavirin. Compounds 3a, 3b, 3c, 3d, and 3e have binding score energy values −7.43, −7.34, −7.34, −8.22, and −7.34, respectively. It disclosed that all of them have higher values than ribavirin. Moreover, compound 3d has higher binding score than chloroquine. Therefore, compound 3d appeared as the most active one for 4OW0 protein.

The binding score energy results of same series toward 5CE1 protein given in Table 8 exhibited that compounds 2a, 2b, 2c, 2d, and 2e have binding score energy values of −6.46, −6.5, −6.74, −7.16, and −6.93, respectively, and compounds 3a, 3b, 3c, 3d, and 3e represented docking score of −6.72, −6.77, −6.69, −7.54, and −7, respectively. All of the docking scores of coumarin series are higher than the docking score for ribavirin, although compounds 3d and 3e afforded higher score than Umifenovir; in addition, compound 3d scored higher than camostat and chloroquine. The docking score of the same series for 6NUR protein displayed in Table 10 showed that compounds 2a, 2b, 2c, 2d, and 2e have binding score energy values of −5.94, −6.06, −6.16, −6.86, and −6.57, respectively, and compounds 3a, 3b, 3c, 3d, and 3e represent docking score of −6, −6.17, −6.34, −7.12, and −6.69. All the compounds in this series are showing binding score higher than ribavirin, and compounds 3d and 3e exhibit higher docking score than chloroquine and Umifenovir. Conclusively, the study results reveal that compound 3d emerges as the most effective compound toward all the proteins examined.

Table 8

Docking score and energy of the compounds and 5CE1 protein

Compound no. S rmsd_refine E_conf E_place E_score1 E_refine E_score2
1a −6.48 1.11 −14.22 −75.53 −9.59 −32.73 −6.48
1b −6.53 1.83 −20.68 −57.45 −10.08 −36.55 −6.53
1c −7.05 2.34 9.97 −78.79 −9.52 −35.91 −7.05
1d −6.73 1.37 6.49 −74.55 −9.82 −35.03 −6.73
1e −6.43 0.97 −23.66 −67.79 −9.63 −29.24 −6.43
2a −6.46 1.57 23.37 −60.65 −9.24 −34.86 −6.46
2b −6.50 1.41 18.86 −63.26 −9.44 −36.39 −6.50
3a −6.72 1.55 −17.08 −58.77 −10.79 −38.19 −6.72
3b −6.77 1.16 −35.33 −90.39 −10.52 −38.65 −6.77
2c −6.74 1.05 1.50 −70.51 −9.54 −36.12 −6.74
2d −7.16 1.14 4.68 −45.65 −11.42 −37.29 −7.16
2e −6.93 1.60 32.84 −50.03 −9.70 −36.10 −6.93
3c −6.93 1.41 −47.84 −88.78 −10.26 −39.89 −6.93
3d −7.54 1.55 −50.83 −63.86 −10.66 −44.50 −7.54
3e −7.00 2.79 −37.03 −43.63 −10.07 −37.07 −7.00
Compound no. S rmsd_refine E_conf E_place E_score1 E_refine E_score2
Umifenovir −6.88 2.06 70.21 −50.29 −9.66 −39.44 −6.88
Chloroquine −7.28 1.82 −38.19 −62.48 −9.21 −35.43 −7.28
Camostat −7.47 1.79 −120.35 −62.38 −10.36 −37.85 −7.47
Remdesivir −8.46 2.09 −28.96 −52.64 −10.44 −51.84 −8.46
Ribavirin −5.96 1.00 152.47 −64.15 −9.68 −34.52 −5.96
Lopinavir −8.26 1.81 −67.22 −76.21 −9.74 −50.19 −8.26

Although 3d has no measurable interactions with the receptors of 1O86 as noticed in Table 1, it actually has a significant docking score and its value is near to chloroquine as shown in Table 2. While 3d is bonded to the receptors of 2GTB, at N-Gly 143(A) by H-acceptor, which seems to be like remdesivir, ribavirin, and Umifenovir; and all of them are also bonded by hydrogen acceptor (Table 3). The docking score of 3d proved that it has higher activity than Umifenovir, chloroquine, camostat, and ribavirin (Table 4).

It is noticed the interaction between compound 3d and protein WO40 happens at the same fragment NZ LYS 158 like remdesivir by pi-cation, and at the fragment NH1 ARG 167-B like ribavirin (Table 6); and it has high docking score values when compared to chloroquine and ribavirin.

Compound 3d interacted with 5CE1 at fragments CYS 188(A) by H-donor and GLY 52(A) by H-acceptor, although none of the tested references showed any interactions at these fragments but the tested compound 3d has a docking score of −7.54, which is higher than that of Umifenovir, chloroquine, camostat, and ribavirin (Tables 7 and 8).

The binding site interaction between 3d and 6NUR happens at ARG 553(A) like camostat and SER 682(A) like remdesivir, and all of them are bonded by pi-H. The docking score of compounds 3d is −7.12, which is higher than Umifenovir, chloroquine, and ribavirin (Tables 9 and 10).

Table 9

Interaction table between the compounds and the chosen standard antiviral with 6NUR protein

Ligand Receptor Interaction Distance E (kcal/mol)
1a N 8 NH1 ARG 624 (A) H-acceptor 3.77 −0.6
O 20 NE ARG 555 (A) H-acceptor 3.03 −3.0
N 21 NZ LYS 545 (A) H-acceptor 3.19 −1.6
6-Ring N THR 556 (A) pi-H 3.98 −4.9
6-Ring N SER 682 (A) pi-H 4.70 −1.3
1b C 24 O THR 680 (A) H-donor 3.32 −0.6
N 8 NH1 ARG 624 (A) H-acceptor 3.24 −0.9
N 9 NH1 ARG 624 (A) H-acceptor 3.19 −2.8
N 9 NH2 ARG 624 (A) H-acceptor 3.36 −0.8
O 20 NE ARG 555 (A) H-acceptor 3.05 −5.4
O 33 NZ LYS 676 (A) H-acceptor 3.40 −2.4
6-Ring NH1 ARG 553 (A) pi-cation 4.94 −1.2
6-Ring N THR 556 (A) pi-H 3.83 −0.6
1c No measurable interactions
1d O 20 NH2 ARG 553 (A) H-acceptor 3.24 −0.8
N 21 NZ LYS 545 (A) H-acceptor 3.29 −4.0
N 21 NH2 ARG 555 (A) H-acceptor 3.33 −2.6
6-Ring N THR 556 (A) pi-H 4.77 −0.5
6-Ring NH1 ARG 624 (A) pi-cation 3.59 −0.6
1e N 21 NH1 ARG 553 (A) H-acceptor 3.31 −3.6
N 21 NH2 ARG 553 (A) H-acceptor 3.69 −0.5
O 32 NZ LYS 676 (A) H-acceptor 3.00 −9.5
2a C 21 OD2 ASP 623 (A) H-donor 3.52 −0.7
O 20 N THR 556 (A) H-acceptor 3.13 −0.6
2b C 21 OD2 ASP 623 (A) H-donor 3.50 −0.6
S 30 O ALA 554 (A) H-donor 3.54 −0.8
O 20 N THR 556 (A) H-acceptor 3.12 −0.6
3a 6-Ring NH1 ARG 624 (A) pi-cation 3.91 −0.8
3b 6-Ring NH1 ARG 624 (A) pi-cation 3.94 −0.9
2c 6-Ring NH1 ARG 624 (A) pi-cation 3.83 −2.4
6-Ring NH2 ARG 624 (A) pi-cation 4.71 −0.5
2d O 16 N THR 556 (A) H-acceptor 2.98 −2.0
6-Ring CD ARG 553 (A) pi-H 4.40 −0.9
6-Ring N SER 682 (A) pi-H 4.47 −1.4
2e C 21 OD2 ASP 623 (A) H-donor 3.60 −0.6
O 20 N THR 556 (A) H-acceptor 3.11 −0.6
3c 6-Ring NH1 ARG 624 (A) pi-cation 3.91 −0.8
3d O 16 N THR 556 (A) H-acceptor 2.96 −2.1
6-Ring CD ARG 553 (A) pi-H 4.38 −0.9
6-Ring N SER 682 (A) pi-H 4.46 −1.5
3e O 16 N THR 556 (A) H-acceptor 3.15 −1.0
6-Ring NH1 ARG 624 (A) pi-cation 3.98 −0.8
Umifenovir 5-Ring NH1 ARG 553 (A) pi-cation 3.46 −1.1
6-Ring NH1 ARG 624 (A) pi-cation 3.53 −1.1
Chloroquine CL 1 NZ LYS 621 (A) H-acceptor 3.48 −1.1
N 34 NH1 ARG 624 (A) H-acceptor 3.37 −2.7
Camostat O 11 N SER 682 (A) H-acceptor 3.00 −0.6
6-Ring CD ARG 553 (A) pi-H 4.04 −0.6
Remdesivir N 64 O THR 680 (A) H-donor 3.34 −1.1
O 15 NZ LYS 621 (A) H-acceptor 2.89 −9.3
6-Ring CB SER 682 (A) pi-H 3.71 −0.9
Ribavirin C 6 OD2 ASP 623 (A) H-donor 3.31 −1.0
N 23 OE2 GLU 665 (A) H-donor 3.25 −1.4
O 8 NH1 ARG 624 (A) H-acceptor 2.79 −2.1
O 26 NZ LYS 676 (A) H-acceptor 2.91 −2.1
5-Ring CB ALA 558 (A) pi-H 3.54 −0.9
Lopinavir 6-Ring NE ARG 555 (A) pi-cation 4.52 −1.7
6-Ring NH2 ARG 555 (A) pi-cation 4.26 −2.1
6-Ring NH1 ARG 624 (A) pi-cation 3.60 −1.1
6-Ring CA SER 681 (A) pi-H 4.46 −0.5
Table 10

Docking score and energy of the compounds and 6NUR protein

Compound no. S rmsd_refine E_conf E_place E_score1 E_refine E_score2
1a −6.19 0.92 −11.33 −138.94 −12.14 −23.58 −6.19
1b −6.70 1.36 6.12 −102.83 −12.48 −28.03 −6.70
1c −6.88 2.38 23.19 −56.84 −11.39 −30.46 −6.88
1d −6.40 1.53 11.56 −63.71 −10.14 −15.32 −6.40
1e −6.26 1.24 −26.82 −84.84 −10.15 −33.66 −6.26
2a −5.94 1.38 26.20 −57.22 −9.38 −29.97 −5.94
2b −6.06 0.99 17.81 −66.62 −9.75 −30.92 −6.06
3a −6.00 1.71 −10.63 −64.41 −10.80 −23.99 −6.00
3b −6.17 1.73 −29.09 −58.52 −10.26 −25.11 −6.17
2c −6.16 1.05 5.21 −73.01 −9.54 −31.32 −6.16
2d −6.86 1.08 5.26 −62.29 −10.72 −28.95 −6.86
2e −6.57 1.58 33.15 −63.19 −9.77 −34.42 −6.57
3c −6.34 1.87 −44.54 −57.46 −10.78 −27.65 −6.34
3d −7.12 1.52 −46.93 −53.15 −9.62 −28.17 −7.12
3e −6.69 2.16 −32.68 −75.00 −11.01 −32.78 −6.69
Compound no. S rmsd_refine E_conf E_place E_score1 E_refine E_score2
Umifenovir −6.54 2.05 64.49 −50.30 −9.62 −36.26 −6.54
Chloroquine −6.82 3.10 −43.44 −54.45 −8.96 −32.20 −6.82
Camostat −7.19 1.97 −121.40 −70.96 −11.20 −40.19 −7.19
Remdesivir −8.42 2.60 −46.00 −85.37 −10.72 −50.77 −8.42
Ribavirin −5.48 1.23 150.97 −72.87 −12.19 −12.27 −5.48
Lopinavir −8.83 1.59 −49.27 −30.42 −9.80 −42.16 −8.83

3.1 Docking of compounds 1a–e, 2a–e, and 3a–e with 1O86 protein by MOE in comparison with different antiviral compounds

Figure 3 2D-Docking of the compounds and the chosen standard antiviral with 1O86 protein.
Figure 3

2D-Docking of the compounds and the chosen standard antiviral with 1O86 protein.

3.2 Docking of compounds 1a–e, 2a–e, and 3a–e with 2GTB protein by MOE in comparison with different antiviral compounds

Figure 4 2D-Docking of the compounds and chosen standard antiviral with 2GTB protein.
Figure 4

2D-Docking of the compounds and chosen standard antiviral with 2GTB protein.

3.3 Docking of compounds 1a–e, 2a–e, and 3a–e with 4OW0 protein by MOE in comparison with different antiviral compounds

Figure 5 2D-Docking of the compounds and the chosen standard antiviral with 4OW0 protein.
Figure 5

2D-Docking of the compounds and the chosen standard antiviral with 4OW0 protein.

3.4 Docking of compounds 1a–e, 2a–e, and 3a–e with 5CE1 protein by MOE in comparison with different antiviral compounds

See Figure 6.

Figure 6 2D-Docking of the compounds and the chosen standard antiviral with 5CE1 protein.
Figure 6

2D-Docking of the compounds and the chosen standard antiviral with 5CE1 protein.

3.5 Docking of compounds 1a–e, 2a–e, and 3a–e with 6NUR protein by MOE in comparison with different antiviral compounds

See Figure 7.

Figure 7 2D-Docking of the compounds and the chosen standard antiviral with 6NUR protein.
Figure 7

2D-Docking of the compounds and the chosen standard antiviral with 6NUR protein.

4 Conclusion

The purpose of this study is to gauge the binding affinity of the active compounds within the target protein that plays a task in the method of virus entry in host cells, virus replication, and therefore the in silico process of virus maturation in host cells. Of the 15 compounds of two prepared series of 2-pyridone derivatives and coumarin derivatives, It has been thought that compound no. 3d was the foremost profit one. Compound 3d showed higher activities toward 2GTB, 4OW0, 5CEI, and 6NUR over Umifenovir, chloroquine, camostat, ribavirin, and generally remdesivir. Hopefully, this analysis will contribute to the discovery of a drug for the COVID-19 antiviral.

tel: +966554156900

  1. Funding: The author thanked the Deanship of Scientific Research, Taif University, KSA, for funding the research work. The fund was obtained on behalf of COVID-19 projects, Project Number 1-441-20.

  2. Author contributions: Dr. Mostafa performed MOE studies. Dr. Magda interpreted the results obtained and wrote and reviewed the final version. Dr. Amena wrote the draft article by collecting literature review. Dr. Abuzar edited the article for English and checked plagiarism.

  3. Conflict of interest: The authors have no conflict of interest.

  4. Data availability statement: The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2020-09-22
Revised: 2021-01-13
Accepted: 2021-01-15
Published Online: 2021-03-03

© 2021 Magda H. Abdellatiif et al., published by De Gruyter

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

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https://doi.org/10.1515/chem-2021-0024
Schlagwörter für diesen Artikel
MOE; molecular docking; COVID-19; pyridones; coumarin
Creative Commons
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Artikel in diesem Heft

  1. Regular Articles
  2. Qualitative and semi-quantitative assessment of anthocyanins in Tibetan hulless barley from different geographical locations by UPLC-QTOF-MS and their antioxidant capacities
  3. Effect of sodium chloride on the expression of genes involved in the salt tolerance of Bacillus sp. strain “SX4” isolated from salinized greenhouse soil
  4. GC-MS analysis of mango stem bark extracts (Mangifera indica L.), Haden variety. Possible contribution of volatile compounds to its health effects
  5. Influence of nanoscale-modified apatite-type calcium phosphates on the biofilm formation by pathogenic microorganisms
  6. Removal of paracetamol from aqueous solution by containment composites
  7. Investigating a human pesticide intoxication incident: The importance of robust analytical approaches
  8. Induction of apoptosis and cell cycle arrest by chloroform fraction of Juniperus phoenicea and chemical constituents analysis
  9. Recovery of γ-Fe2O3 from copper ore tailings by magnetization roasting and magnetic separation
  10. Effects of different extraction methods on antioxidant properties of blueberry anthocyanins
  11. Modeling the removal of methylene blue dye using a graphene oxide/TiO2/SiO2 nanocomposite under sunlight irradiation by intelligent system
  12. Antimicrobial and antioxidant activities of Cinnamomum cassia essential oil and its application in food preservation
  13. Full spectrum and genetic algorithm-selected spectrum-based chemometric methods for simultaneous determination of azilsartan medoxomil, chlorthalidone, and azilsartan: Development, validation, and application on commercial dosage form
  14. Evaluation of the performance of immunoblot and immunodot techniques used to identify autoantibodies in patients with autoimmune diseases
  15. Computational studies by molecular docking of some antiviral drugs with COVID-19 receptors are an approach to medication for COVID-19
  16. Synthesis of amides and esters containing furan rings under microwave-assisted conditions
  17. Simultaneous removal efficiency of H2S and CO2 by high-gravity rotating packed bed: Experiments and simulation
  18. Design, synthesis, and biological activities of novel thiophene, pyrimidine, pyrazole, pyridine, coumarin and isoxazole: Dydrogesterone derivatives as antitumor agents
  19. Content and composition analysis of polysaccharides from Blaps rynchopetera and its macrophage phagocytic activity
  20. A new series of 2,4-thiazolidinediones endowed with potent aldose reductase inhibitory activity
  21. Assessing encapsulation of curcumin in cocoliposome: In vitro study
  22. Rare norisodinosterol derivatives from Xenia umbellata: Isolation and anti-proliferative activity
  23. Comparative study of antioxidant and anticancer activities and HPTLC quantification of rutin in white radish (Raphanus sativus L.) leaves and root extracts grown in Saudi Arabia
  24. Comparison of adsorption properties of commercial silica and rice husk ash (RHA) silica: A study by NIR spectroscopy
  25. Sodium borohydride (NaBH4) as a high-capacity material for next-generation sodium-ion capacitors
  26. Aroma components of tobacco powder from different producing areas based on gas chromatography ion mobility spectrometry
  27. The effects of salinity on changes in characteristics of soils collected in a saline region of the Mekong Delta, Vietnam
  28. Synthesis, properties, and activity of MoVTeNbO catalysts modified by zirconia-pillared clays in oxidative dehydrogenation of ethane
  29. Synthesis and crystal structure of N,N′-bis(4-chlorophenyl)thiourea N,N-dimethylformamide
  30. Quantitative analysis of volatile compounds of four Chinese traditional liquors by SPME-GC-MS and determination of total phenolic contents and antioxidant activities
  31. A novel separation method of the valuable components for activated clay production wastewater
  32. On ve-degree- and ev-degree-based topological properties of crystallographic structure of cuprite Cu2O
  33. Antihyperglycemic effect and phytochemical investigation of Rubia cordifolia (Indian Madder) leaves extract
  34. Microsphere molecularly imprinted solid-phase extraction for diazepam analysis using itaconic acid as a monomer in propanol
  35. A nitric oxide-releasing prodrug promotes apoptosis in human renal carcinoma cells: Involvement of reactive oxygen species
  36. Machine vision-based driving and feedback scheme for digital microfluidics system
  37. Study on the application of a steam-foam drive profile modification technology for heavy oil reservoir development
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  39. Preparation of composite soybean straw-based materials by LDHs modifying as a solid sorbent for removal of Pb(ii) from water samples
  40. Synthesis and spectral characterizations of vanadyl(ii) and chromium(iii) mixed ligand complexes containing metformin drug and glycine amino acid
  41. In vitro evaluation of lactic acid bacteria with probiotic activity isolated from local pickled leaf mustard from Wuwei in Anhui as substitutes for chemical synthetic additives
  42. Utilization and simulation of innovative new binuclear Co(ii), Ni(ii), Cu(ii), and Zn(ii) diimine Schiff base complexes in sterilization and coronavirus resistance (Covid-19)
  43. Phosphorylation of Pit-1 by cyclin-dependent kinase 5 at serine 126 is associated with cell proliferation and poor prognosis in prolactinomas
  44. Molecularly imprinted membrane for transport of urea, creatinine, and vitamin B12 as a hemodialysis candidate membrane
  45. Optimization of Murrayafoline A ethanol extraction process from the roots of Glycosmis stenocarpa, and evaluation of its Tumorigenesis inhibition activity on Hep-G2 cells
  46. Highly sensitive determination of α-lipoic acid in pharmaceuticals on a boron-doped diamond electrode
  47. Synthesis, chemo-informatics, and anticancer evaluation of fluorophenyl-isoxazole derivatives
  48. In vitro and in vivo investigation of polypharmacology of propolis extract as anticancer, antibacterial, anti-inflammatory, and chemical properties
  49. Topological indices of bipolar fuzzy incidence graph
  50. Preparation of Fe3O4@SiO2–ZnO catalyst and its catalytic synthesis of rosin glycol ester
  51. Construction of a new luminescent Cd(ii) compound for the detection of Fe3+ and treatment of Hepatitis B
  52. Investigation of bovine serum albumin aggregation upon exposure to silver(i) and copper(ii) metal ions using Zetasizer
  53. Discoloration of methylene blue at neutral pH by heterogeneous photo-Fenton-like reactions using crystalline and amorphous iron oxides
  54. Optimized extraction of polyphenols from leaves of Rosemary (Rosmarinus officinalis L.) grown in Lam Dong province, Vietnam, and evaluation of their antioxidant capacity
  55. Synthesis of novel thiourea-/urea-benzimidazole derivatives as anticancer agents
  56. Potency and selectivity indices of Myristica fragrans Houtt. mace chloroform extract against non-clinical and clinical human pathogens
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Heruntergeladen am 30.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/chem-2021-0024/html
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