Exploring structurally diverse plant secondary metabolites as a potential source of drug targeting different molecular mechanisms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pathogenesis: An in silico approach

Abstract

Plants are endowed with a large pool of structurally diverse small molecules known as secondary metabolites. Present study aims to virtually screen these plant secondary metabolites (PMS) for their possible anti-SARS-CoV-2 properties targeting four protein/enzymes which determines viral pathogenesis. Results of molecular docking and data analysis revealed a unique pattern of structurally similar PSM interacting with the target protein. Among the top-ranked PSM with lower binding energy, >50% were triterpenoids against viral spike protein, >32% were flavonoids and their glycoside against Human transmembrane serine protease, >16% were flavonol glycosides and >16% were Anthocyanidine against viral main protease and >13% were flavonol glycoside against viral RNA dependet RNA polymerase. The primary concern about these PSM is their bioavailability. However, several PSM recorded higher bioavailability score and found fulfilling drug-likeness characters as per Lipinski's rule. Natural occurrence, biotransformation, bioavailability of selected PSM and their interaction with the target site of selected proteins were discussed in detail. Further, we hypothesized the use of selected PSM to cure the COVID-19 by inhibiting the process of viral host cell recognition and replication in host cell. However, these PSM needs thorough in vitro and in vivo evaluation before taking them to clinical trials.

Pomegranate Peel Extract as an Inhibitor of SARS-CoV-2 Spike Binding to Human ACE2 Receptor (in vitro): A Promising Source of Novel Antiviral Drugs

“…Through molecular-docking studies, Khalifa et al (2020) found that some hydrolysable tannins, in particular pedunculagin, tercatain, and castalin, might serve as potential inhibitors of SARS-CoV-2 as they were able to specifically bind the 3CL protease catalytic site. In parallel studies, Hariprasad et al (2020) tested the virtual interaction between many plant secondary metabolites and four target proteins involved in COVID-19, the host protease TMPRSS2 and the three virus proteins, Spike, main protease, and RNA-dependent RNA polymerase, and predicted among the class of triterpenoids the most active compounds in blocking the Spike-binding site. Bhatia et al (2020) also identified PC among dietary polyphenols as a potential inhibitor of Spike and other viral proteases.…”

A pomegranate peel extract as inhibitor of SARS-CoV-2 Spike binding to human ACE2 (in vitro): a promising source of novel antiviral drugs

“…In parallel studies Hariprasad et al 2020 tested the virtual interaction between many plant secondary metabolites and four target proteins involved in Covid-19, the host protease TMPRSS2 and the three virus proteins, Spike, Main Protease and RNA-dependent RNA polymerase, and predicted among the class of triterpenoids the most active compounds in blocking the Spike binding site 61 . Bhatia et al 37 (2020) also identified PC among dietary polyphenols as potential inhibitor of Spike and other viral proteases.…”