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Medicinal and therapeutic potential of withanolides from Withania somnifera against COVID-19

TLDR
A review highlights the medicinal and therapeutic potential of withanolides against COVID-19 and identifies WFA as one of the most interesting naturally occurring bioactive compounds that possess potent anti-tumorigenic, antiinflammatory, pro-apoptotic, anti-angiogenic, and anti-invasive activities.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the potentially fatal coronavirus disease 2019 (COVID-19), has currently affected over 87 million people with worldwide deaths nearing 1 9 million Amidst the developing vaccines and effective therapies, there is a need to develop alternative and supportive strategies for ameliorating the effects of SARS-CoV-2 infections in humans and treat COVID-19 patients Several medicinal plants and herbs contain useful phytochemicals, which are being explored to develop medicines and drugs to counter the COVID-19 pandemic Withania somnifera is a medicinal herb of growing importance that is extensively utilized in Ayurveda The medicinal attributes of W somnifera are owing to a broad range of bioactive secondary metabolites including steroidal lactones [withanone, withanolide D, withanolide A, and withaferin A (WFA)] Among these, WFA is one of the most interesting naturally occurring bioactive compounds that possess potent anti-tumorigenic, antiinflammatory, pro-apoptotic, anti-angiogenic, and anti-invasive activities It might bind to SARS-CoV-2 S protein and alter the S protein, thereby hindering its access into the host cells Withanone and Withanoside V can impede the functional activities of SARS-CoV-2 main protease (Mpro) Withanolides have been found to control cytokine secretions during infection and could alleviate the cytokine storm in the lungs The combined use of withanolides are several other drugs or therapeutic modalities, such as hydroxychloroquine and dexamethasone, has been demonstrated as an efficient strategy to improve the effectiveness of standard chemotherapy or design a robust therapeutic regime for COVID-19 treatment Nevertheless, exhaustive research efforts are required to explore the anti-inflammatory and immunomodulatory potentialities of withanolides for alleviating the severity of the disease during SARS-CoV-2 infections This review highlights the medicinal and therapeutic potential of withanolides against COVID-19 © 2021 Manish Dhawan et al This is an open access article distributed under the terms of the Creative Commons Attribution 4 0 International License (https://creativecommons org/licenses/by/4 0/)

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Citations
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A novel 2019: Coronavirus

TL;DR: This review summarizes both classical and contemporary discoveries in the study of the molecular biology of these infectious agents, with particular emphasis on the nature and recognition of viral receptors, viral RNA synthesis, and the molecular interactions governing viral assembly.
Journal Article

Medicinal Plants as Sources of Active Molecules Against COVID-19. LID - 1189

TL;DR: Benarba et al. as mentioned in this paper reviewed the recent findings regarding the use of natural products to prevent or treat COVID-19 infection and discussed mechanisms responsible for this preventive or therapeutic effect.

Withaferin A: a potential therapeutic agent against COVID-19 infection

TL;DR: WFA demonstrates real potential as a therapeutic agent to treat or prevent the spread of COVID-19 due to the reported interference in viral S-protein to host receptor binding and its lack of effect on ACE2 expression in the lungs.
References
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TL;DR: High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS -CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues.
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TL;DR: This study conducted a retrospective multicenter study of 68 death cases and 82 discharged cases with laboratory-confirmed infection of SARS-CoV-2 and confirmed that some patients died of fulminant myocarditis, which is characterized by a rapid progress and a severe state of illness.
Journal ArticleDOI

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TL;DR: The interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression is described and the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation are highlighted.
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TL;DR: This study determines the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2 and sheds light on the structural features that increase its binding affinity to ACE2.
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