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

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/).