Identification of bioactive molecule from Withania somnifera (Ashwagandha) as SARS-CoV-2 main protease inhibitor

Abstract

SARS-CoV-2 is the causative agent of COVID-19 and has been declared as pandemic disease by World Health Organization. Lack of targeted therapeutics and vaccines for COVID-2019 have triggered the scientific community to develop new vaccines or drugs against this novel virus. Many synthetic compounds and antimalarial drugs are undergoing clinical trials. The traditional medical practitioners widely use Indian medicinal plant Withania somnifera (Ashwagandha) natural constituents, called withanolides for curing various diseases. The main protease (M pro ) of SARS-CoV-2 plays a vital role in disease propagation by processing the polyproteins which are required for its replication. Hence, it denotes a significant target for drug discovery. In the present study, we evaluate the potential of 40 natural chemical constituents of Ashwagandha to explore a possible inhibitor against main protease of SARS-CoV-2 by adopting the computational approach. The docking study revealed that four constituents of Ashwagandha; Withanoside II (-11.30 Kcal/mol), Withanoside IV (-11.02 Kcal/mol), Withanoside V (-8.96 Kcal/mol) and Sitoindoside IX (-8.37 Kcal/mol) exhibited the highest docking energy among the selected natural constituents. Further, MD simulation study of 100 ns predicts Withanoside V possess strong binding affinity and hydrogen-bonding interactions with the protein active site and indicates its stability in the active site. The binding free energy score also correlates with the highest score of −87.01 ± 5.01 Kcal/mol as compared to other selected compounds. In conclusion, our study suggests that Withanoside V in Ashwagandha may be serve as a potential inhibitor against M pro of SARS-CoV-2 to combat COVID-19 and may have an antiviral effect on nCoV. Communicated by Ramaswamy H. Sarma

Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation

“…It is also predicted that withanone and withaferin-A can interact with transmembrane protease serine 2 (TMPRSS2), thereby potentially could block the entry of SARS-CoV-2 into host cells [75]. A combination of withanone and caffeic acid phenethyl ester [76] or withanoside-V [77] has also been predicted to inhibit SARS-CoV-2 activity by interacting with its main protease (M pro ). Anti-viral properties of ursolic acid [78] and betulinic acid [79] have been reported, with ursolic acid also inhibiting M pro under in silico conditions [80].…”

Computer aided identification of potential SARS CoV-2 main protease inhibitors from diterpenoids and biflavonoids of Torreya nucifera leaves

“…In order to rank different proposed SARS CoV-2 Mpro inhibitors, the binding free energy of these inhibitors was compared with the DG bind of "Mpro-N3 interaction" (Alamri et al, 2020;Ghosh et al, 2020aGhosh et al, , 2020bKumar et al, 2020;Tripathi et al, 2020). Many proposed Mpro inhibitors including phytochemicals (such as withanone, caffeic acid, epigallocatechin gallate, epicatechingallate, gallocatechin-3-gallate etc.…”

“…Furthermore, various phytochemicals are also proposed as the SARS CoV-2 main protease inhibitors through screening and structure-based design approach (Gorla et al, 2020;Gurung et al, 2020;Mazzini et al, 2020). In recent times, it has been found that plant-derived polyphenols can serve as potent SARS CoV-2 Mpro inhibitors (Bhardwaj et al, 2020;Ghosh et al, 2020aGhosh et al, , 2020bTripathi et al, 2020). Our group has identified three polyphenols from green tea [epigallocatechin gallate (EGCG), epicatechingallate (ECG) and gallocatechin-3-gallate (GCG)] can inhibit the catalytic activity of SARS CoV-2 Mpro (Ghosh et al, 2020a).…”

Molecular modeling study of tectoquinone and acteoside from Tectona grandis linn: a new SARS-CoV-2 main protease inhibitor against COVID-19

“…Protein preparation was done by using the protein preparation wizard of Schr€ odinger maestro, where hydrogen atoms were added and water molecules were removed. Sidechains and loops were built using the prime module (Madhavi Sastry et al, 2013) and the ligand preparation was done by using the Ligprep module (Tripathi et al, 2020). The OPLS-2005 force field was used for further optimization and minimization of the protein and ligand structures.…”