Repurposing of phytomedicine-derived bioactive compounds with promising anti-SARS-CoV-2 potential: Molecular docking, MD simulation and drug-likeness/ADMET studies

Abstract

In view of the potential of traditional plant-based remedies (or phytomedicines) in the management of COVID-19, the present investigation was aimed at finding novel anti-SARS-CoV-2 molecules by in silico screening of bioactive phytochemicals (database) using computational methods and drug repurposing approach. A total of 160 compounds belonging to various phytochemical classes (flavonoids, limonoids, saponins, triterpenoids, steroids etc.) were selected (as initial hits) and screened against three specific therapeutic targets (Mpro/ 3CLpro, PLpro and RdRp) of SARS-CoV-2 by docking, molecular dynamics simulation and drug-likeness/ADMET studies. From our studies, six phytochemicals were identified as notable ant-SARS-CoV-2 agents (best hit molecules) with promising inhibitory effects effective against protease (Mpro and PLpro) and polymerase (RdRp) enzymes. These compounds are namely, ginsenoside Rg2, saikosaponin A, somniferine, betulinic acid, soyasapogenol C and azadirachtin A. On the basis of binding modes and dynamics studies of protein-ligand intercations, ginsenoside Rg2, saikosaponin A, somniferine were found to be the most potent ( in silico ) inhibitors potentially active against Mpro, PLpro and RdRp, respectively. The present investigation can be directed towards further experimental studies in order to confirm the anti-SARS-CoV-2 efficacy along with toxicities of identified phytomolecules.

Silybin phytosome attenuates cerebral ischemia‐reperfusion injury in rats by suppressing oxidative stress and reducing inflammatory response: In vivo and in silico approaches

“…AutoDock Vina relies on both empirical and knowledge‐based scoring functions. [ 24 ] PyRx virtual screening tool utilizes AutoDock Vina for molecular docking and was used for the docking study (http://pyrx.sourceforge.net).…”

Multi-target mechanisms against coronaviruses of constituents from Chinese Dagang Tea revealed by experimental and docking studies

“…Structure-activity relationship exploration of betulinic acid derivatives yielded a strong inhibitor of HCoV-229E replication via the nsp15 endoribonuclease ( Stevaert et al, 2021 ). Betulinic acid was reported to interact strongly with the PLpro from docking and MD simulation studies ( Rudrapal et al, 2022 ), but the inhibition activity and structural modification of betulinic acid against PLpro have not been further studied as far as we know. The affinity and the inhibition activity of betulinic acid ( 1 ) binding to N7-MTase have not been studied as far as we know.…”

Structural Elucidation of Rift Valley Fever Virus L Protein towards the Discovery of Its Potential Inhibitors

“…The RdRp has been explored in SARS-CoV-2 for dynamics in the presence of a variety of drug molecules. The studies have found several leads that experience stable conformational dynamics and showed significant intermolecular stability with enzyme's active pockets [98][99][100]. However, RdRp from RVFV is not investigated so far, making the findings of the current study interesting for experimentalists to test them in in vivo and in vitro validation.…”