Herbo-mineral formulation, Divya-Swasari-Vati averts SARS-CoV-2 pseudovirus entry into human alveolar epithelial cells by interfering with spike protein-ACE 2 interaction and IL-6/TNF-α /NF-κB signaling
Authors
Acharya Balkrishna
Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India
Sudeep Goswami
Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India
Hoshiyar Singh
Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India
Vivek Gohel
Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India
Rishabh Dev
Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India
Swati Haldar
Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India
Anurag Varshney
Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India
The herbo-mineral formulation, Divya-Swasari-Vati (DSV), is a well-known Ayurvedic medication for respiratory ailments. In a recent pre-clinical study, DSV rescued humanized zebrafish from SARS-CoV-2 S-protein-induced pathologies. This merited for an independent evaluation of DSV as a SARS-CoV-2 entry inhibitor in the human host cell and its effectiveness in ameliorating associated cytokine production. The ELISA-based protein-protein interaction study showed that DSV inhibited the interactions of recombinant human ACE 2 with three different variants of S proteins, namely, Smut 1 (the first reported variant), Smut 2 (W436R variant) and Smut 3 (D614G variant). Entry of recombinant vesicular stomatitis SARS-CoV-2 (VSVppSARS-2S) pseudovirus, having firefly luciferase and EGFP reporters, was assessed through luciferase assay and fluorescent microscopy. DSV exhibited dose-dependent inhibition of VSVppSARS-2S pseudovirus entry into human lung epithelial A549 cells and also suppressed elevated levels of secreted pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) induced by viral infection mimicking Poly I:C-, S-protein- and VSVppSARS-2S pseudovirus. In human immune cells, DSV also moderated TNF-α-mediated NF-κB induction, in a dose-dependent manner. The observed anti-viral effect of DSV against SARS-CoV-2 is attributable to the presence of different metabolites Summarily, the observations from this study biochemically demonstrated that DSV interfered with the interaction between SARS-CoV-2 S-protein and human ACE 2 receptor which consequently, inhibited viral entry into the host cells and concomitant induction of inflammatory response.
Keywords: Divya-Swasari-Vati (DSV), SARS-CoV-2, pseudovirus, spike protein, ACE 2, proinflammatory cytokines
Author Biographies
Acharya Balkrishna, Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India
Department of Allied and Applied Sciences, University of Patanjali, Haridwar, Uttarakhand, India
Anurag Varshney, Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India
Special Centre for Systems Medicine, Jawaharlal Nehru University, New Delhi, India
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