Withanone from Withania somnifera May Inhibit Novel Coronavirus (COVID-19) Entry by Disrupting Interactions between Viral S-Protein Receptor Binding Domain and Host ACE2 Receptor

Abstract

Background Newly emerged COVID-19 has been shown to engage the host cell ACE2 through its spike protein receptor binding domain (RBD). Here we show that natural phytochemical from a medicinal herb, Withania somnifera, have distinct effects on viral RBD and host ACE2 receptor complex. Methods We employed molecular docking to screen thousands of phytochemicals against the ACE2-RBD complex, performed molecular dynamics (MD) simulation, and estimated the electrostatic component of binding free energy, along with the computation of salt bridge electrostatics. Results We report that W. somnifera compound, Withanone, docked very well in the binding interface of AEC2-RBD complex, and was found to move slightly towards the interface centre on simulation. Withanone significantly decreased electrostatic component of binding free energies of ACE2-RBD complex. Two salt bridges were also identified at the interface; incorporation of Withanone destabilized these salt bridges and decreased their occupancies. We postulate, such an interruption of electrostatic interactions between the RBD and ACE2 would block or weaken COVID-19 entry and its subsequent infectivity. Conclusion Our data, for the first time, show that natural phytochemicals could well be the viable options for controlling COVID-19 entry into host cells, and W. somnifera may be the first choice of herbs in these directions to curb the COVID-19 infectivity.

Antiviral potential of phytoligands against chymotrypsin-like protease of COVID‐19 virus using molecular docking studies: An optimistic approach

“…withanone from Withania somnifera, displayed signi cant docking with the binding interface of ACE2-RBD complex. 49 Sofosbuvir which showed least toxicity in the present study is a prodrug nucleotide analogue and has recently been proposed as an antiviral for the SARS-CoV-2 based on the similarity between the replication mechanisms of the hepatitis C virus and the coronaviruses. .…”

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

“…Recent work has demonstrated that COVID-19 infections have a large immune component and can result in the development of cytokine storm, a potentially life-threatening immune reaction in which the body release too many cytokines into the blood at a rapid rate [28]. Interestingly, at least three independent research groups have suggested that phytochemicals found in the plant Withania somnifera could be developed as a therapeutic agent against COVID-19 infection using molecular docking approaches [29][30][31]. Two of the groups reported that various Withanolides, such as WFA, should be able to bind to the viral S-protein receptor binding domain, thereby blocking or reducing interactions with host ACE2 receptor [29,30].…”

“…Interestingly, at least three independent research groups have suggested that phytochemicals found in the plant Withania somnifera could be developed as a therapeutic agent against COVID-19 infection using molecular docking approaches [29][30][31]. Two of the groups reported that various Withanolides, such as WFA, should be able to bind to the viral S-protein receptor binding domain, thereby blocking or reducing interactions with host ACE2 receptor [29,30]. The third group reported that WFA and a separate withanolide, Withanone, are predicted to interact with the main protease of SARS-CoV-2, although WFA is predicted to have less of a binding a nity than an established N3 protease inhibitor used for baseline docking scores [31].…”

“…Due to this effect, others have suggested that blocking the binding of SARS-CoV-2 to the ACE2 receptor may be a more bene cial strategy to combat the virus than augmenting ACE2 expression, due to its antagonistic effect on AT1R signaling [9]. In line with this rationale, it is within the realm of possibility that WFA can block or impede COVID-19 through interactions with the viral S-protein based upon the molecular docking studies [29,30], without affecting ACE2 expression (as reported in our data) leading to a worsening of the pathological state.…”

Ayurveda botanicals in COVID-19 management: An in silico- multitarget approach

“…In Ayurveda, "Rasayana botanicals" are used for rejuvenation by boosting the immune system and alleviating disease condition 19,20,21 . Of several known botanicals Asparagus racemosus (AR), Tinosporacordifolia (TC), and Withaniasomnifera (WS) are known to modulate the immune system and possess antiviral activities 19,20,22,23,8 .…”