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

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 ent...

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Main Authors: Acharya Balkrishna, Sudeep Goswami, Hoshiyar Singh, Vivek Gohel, Rishabh Dev, Swati Haldar, Anurag Varshney
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.1024830/full
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author Acharya Balkrishna
Acharya Balkrishna
Sudeep Goswami
Hoshiyar Singh
Vivek Gohel
Rishabh Dev
Swati Haldar
Anurag Varshney
Anurag Varshney
Anurag Varshney
author_facet Acharya Balkrishna
Acharya Balkrishna
Sudeep Goswami
Hoshiyar Singh
Vivek Gohel
Rishabh Dev
Swati Haldar
Anurag Varshney
Anurag Varshney
Anurag Varshney
author_sort Acharya Balkrishna
collection DOAJ
description 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.
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spelling doaj.art-546736217fdc47a9bfa3dc77b3d54fb22022-12-22T02:36:00ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.10248301024830Herbo-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 signalingAcharya Balkrishna0Acharya Balkrishna1Sudeep Goswami2Hoshiyar Singh3Vivek Gohel4Rishabh Dev5Swati Haldar6Anurag Varshney7Anurag Varshney8Anurag Varshney9Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, IndiaDepartment of Allied and Applied Sciences, University of Patanjali, Haridwar, Uttarakhand, IndiaDrug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, IndiaDrug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, IndiaDrug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, IndiaDrug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, IndiaDrug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, IndiaDrug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, IndiaDepartment of Allied and Applied Sciences, University of Patanjali, Haridwar, Uttarakhand, IndiaSpecial Centre for Systems Medicine, Jawaharlal Nehru University, New Delhi, IndiaThe 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.1024830/fullDivya-Swasari-Vati (DSV)SARS-CoV-2pseudovirusspike proteinACE 2proinflammatory cytokines
spellingShingle Acharya Balkrishna
Acharya Balkrishna
Sudeep Goswami
Hoshiyar Singh
Vivek Gohel
Rishabh Dev
Swati Haldar
Anurag Varshney
Anurag Varshney
Anurag Varshney
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
Frontiers in Pharmacology
Divya-Swasari-Vati (DSV)
SARS-CoV-2
pseudovirus
spike protein
ACE 2
proinflammatory cytokines
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Divya-Swasari-Vati (DSV)
SARS-CoV-2
pseudovirus
spike protein
ACE 2
proinflammatory cytokines
url https://www.frontiersin.org/articles/10.3389/fphar.2022.1024830/full
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