Withasomniferol C, a new potential SARS-CoV-2 main protease inhibitor from the Withania somnifera plant proposed by in silico approaches

Abstract

Exploring potent herbal medicine candidates is a promising strategy for combating a pandemic in the present global health crisis. In Ayurveda (a traditional medicine system in India), Withania somnifera (WS) is one of the most important herbs and it has been used for millennia as Rasayana (a type of juice) for its wide-ranging health benefits. WS phytocompounds display a broad spectrum of biological activities (such as antioxidant, anticancer and antimicrobial) modulate detoxifying enzymes, and enhance immunity. Inspired by the numerous biological actions of WS phytocompounds, the present investigation explored the potential of the WS phytocompounds against the SARS-CoV-2 main protease (3CLpro). We selected 11 specific withanolide compounds, such as withaphysalin, withasomniferol, and withafastuosin, through manual literature curation against 3CLpro. A molecular similarity analysis showed their similarity with compounds that have an established inhibitory activity against the SARS-CoV-2. In silico molecular docking and molecular dynamics simulations elucidated withasomniferol C (WS11) as a potential candidate against SARS-CoV-2 3CLpro. Additionally, the present work also presents a new method of validating docking poses using the AlteQ method.

Phyto‐therapeutic potential of Withania somnifera: Molecular mechanism and health implications

“…The phytocompounds have a variety of biological functions and improve immunity. Using the innovative AlteQ approach, in silico molecular docking and molecular dynamics simulations were performed, indicating withasomniferol C (WS11) as a significant contender against severe acute respiratory syndrome coronavirus 2 (Kandagalla et al, 2022). One of the studies, proposed the medicinal importance of the W. somnifera (ashwagandha) plant in inhibition of the virus CoVs, including COVID‐19 and Hemagglutinin Esterase glycoprotein (HE) receptors as targets because of having various steroids and alkaloids (Patel et al, 2022).…”

In Silico Identification of a Potential TNF-Alpha Binder Using a Structural Similarity: A Potential Drug Repurposing Approach to the Management of Alzheimer’s Disease

“…Plant-derived compounds have been a focal point in drug discovery for centuries, and recent advances in computational chemistry and molecular modelling have expedited the process of identifying promising drug candidates from natural sources [26,27]. In silico methods have been used to predict the biological activities of plant-derived compounds, thereby speeding up the process of identifying promising drug candidates at a reduced cost [28][29][30]. This is particularly important for developing countries, where plant diversity is high and access to modern drug discovery technologies is limited.…”

The design of compounds with desirable properties – The anti‐HIV case study

“…29,30 Wei et al 31 35,36 Various studies tried to repurpose existing drugs, with special attention given to antiviral drugs and HIV protease inhibitors. [37][38][39][40][41][42][43][44] Motivated by those studies and encouraged by successful designed, validation and application of QSAR model predicting anti-3CLpro activity, 42 for all proposed HIV-1 protease inhibitors their possibility to stop the activity of the 3CLpro will be predicted.…”