Ayurvedic medicines in alleviating the symptoms of SARS-CoV-2 omicron variant in North Indian population: a regional genomic study

To the Editor,

Globally, countless current cases and fatalities are linked to different SARS-CoV-2 strains. Currently, it is generally known that new SARS-CoV-2 mutations are to blame for the host’s heightened virulence, immunological evasion, and transmissibility [1]. While these have been exacerbated by climate change [2], the aforementioned capabilities have been reported to be caused by variations in the SARS-CoV-2 genome, which either encode non-structural proteins (NSPs) or the receptor-binding domains (RBDs) of spike proteins [3]. It has been discovered that a number of alterations (L452R/E484Q) in the RBDs of spike proteins, increase the virus’s already high transmissibility and viral load and confer resistance against neutralization by the host immune system or vaccinations [4]. Furthermore, the E484K mutation accounts for increased resistance to neutralization by antibodies produced following vaccination [5]. Moreover, the GISAID COVSURVER [6] mutation application reported several mutations in the Omicron (BA.2) variant in the Indian population. These mutations included Spikes such as: A27S, D405N, D614G, D796Y, E484A, G142D, G339D, H655Y, K417N, L24del, N440K, N501Y, N679K, N764K, N969K, P25del, P26del, P681H, Q493R, Q498R, Q954H, R408S, S371F, S373P, S375F, S477N, T19I, T376A, T478K, V213G and Y505H mutations. We also found the similarities in many regions of viral genomic structure, including ORF (open reading frame region) regions and NSPs (non-structural proteins). But, unlike mutations in the spike protein areas, the mutations in these regions were do not specifically increase or decrease the virulence. Several medicaments have been proposed and tried amid the pandemic, for both reductions of viral load as well as for alleviating the symptoms following the COVID infection. Though, emphasis has shifted from western medicine to complementary and alternative medicine systems due to the absence of prospective allopathic treatments in the same [7]. Under the clinical study program entitled ‘Efficacy study of Ayurveda dosage forms for the management of COVID-19’ registered in the Clinical Trial Registry – India (Trial ID No. CTRI/2021/09/036380), we found that the herbo-mineral drug, Fifatrol, is a potential option for curtailing the symptoms attributed to SARS-CoV-2 infection. In this clinical trial, oral administration of Fifatrol tablet (610 mg) along with AMRYTAVIR (10 mL) by mixing equal quantity of water and RRAIR-02 one dhupa stick advised for inhalation through mouth and nose, two times in a day and by following precautions of Central Government advisory for 15 days. Samples from the intervention or Fifatrol group and the control group were randomly selected in order to assess the impact of the omicron variation. RT-PCR-positive SARS-CoV-2 patients were receiving the government-recommended medication regimen from the Indian Council for Medical Research (ICMR) made up the control group. In contrast, the Fifatrol group included RT-PCR-positive SARS-CoV-2 patients under a combinational treatment regimen including Fifatrol tablets, Amrytavir syrup, and RRAIR-02 dhupa inhalation. We isolated samples from nasopharynx and oropharynx in both groups to isolate SARS-CoV-2 viral mRNA, followed by processing for lysis and mRNA extraction using a magnetic bead separator. Subsequently, the isolated mRNA was assayed for the presence of SARS-CoV2 N/ORF1ab genes using RT-PCR assay. Then after, the isolated mRNA was subjected to next-generation genome sequencing, and the results were analyzed using bioinformatics tools, such as Pangolin and NextClade. Patients gladly volunteered to share the history of their disease progression and development, as well as immunization status, which was tabulated in Microsoft Excel for tabular and graphical representations. Three patients from the control and intervention (Fifatrol) groups were selected based on their viral load, and the Omicron (BA.2) variant was reported in all of them and was conspicuously corroborated by common mutations such as in Spikes: D614G, N764K, D796Y, Q954H, and N969K, which have been attributed to increased virulence and host change viral oligomerization. The samples collected from the control group reported spike protein mutations, such as T19I(20), L24del, P25del, P26del, A27S, G142D, S477N, T478K, E484A, Q498R, N440K, N501Y, Q493R and Y505H, as shown in Figure 1. Interestingly, the Fifatrol group demonstrated mutations such as Spikes: T19I(20), L24del, P25del, P26del, and A27S, which overlapped with the control group.

Figure 1:

Complex of human ACE2 and spike glycoprotein of SARS-CoV-2 (hACE2 receptor depicted as a green ribbon). List of variations displayed in structure (or of the nearest residue if in loop/termini region).

It is noteworthy that patients under the herbo-mineral drug Fifatrol regimen developed very mild symptoms compared to the control group, which was deprived of the same. Additionally, the control group presented severe-to-grave symptoms, including dyspnoea, prolonged and recurring high-grade fever, anosmia, and dysgeusia. However, patients in the intervention (Fifatrol) group did not present any symptoms that were reported in the control group. The viral genome sequencing revealed no appreciable variations in the Omicron (BA.2) proteins isolated from the patient groups. However, these mutations were positively correlated with viral oligomerization, viral transmissibility, immune evasion, and resistance to neutralization and protection conferred by immunization. While the patients in the intervention (Fifatrol) group did present with symptoms, these were rather mild compared to the control group, which presented with severe symptoms. Thus, this study underscores and validates the potential of fifatrol in alleviating and/or limiting the symptoms precipitated by the Omicron (BA.2) variant. However, more research is required to fully comprehend the mechanism of Ayurvedic medications and their potential to combat unique and emerging SARS-CoV-2 strains.