Repositioning Therapeutics for SARS-CoV-2: Virtual Screening of Plant-based Anti-HIV Compounds as Possible Inhibitors against COVID-19 Viral RdRp

Abstract

Background: Coronavirus disease 2019 (COVID-19) has caused a global pandemic with a high mortality and morbidity rate worldwide. The COVID-19 vaccines that are currently in development or already approved are expected to provide at least some protection against the emerging variants of the virus, but the muta-tions may reduce the efficacy of the existing vaccines. Purified phytochemicals from medicinal plants provide a helpful framework for discovering new therapeutic leads as they have long been employed in traditional medicine to treat many disorders. Objective: The objectives of the study are to exploit the anti-HIV bioactive compounds against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) through molecular docking studies and to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of potential compounds. Methods: Molecular docking was performed to study the interaction of ligands with the target sites of RdRp protein (PDB: 6M71) using AutoDock Vina. The ADMET properties of potential compounds were predicted using the pkCSM platform. Results: A total of 151 phytochemicals derived from the medicinal plants with recognized antiviral activity and 18 anti-HIV drugs were virtually screened against COVID-19 viral RdRp to identify putative inhibitors that facilitate the development of potential anti-COVID-19 drug candidates. The computational studies identified 34 compounds and three drugs inhibiting viral RdRp with binding energies ranging from-10.2 to-8.5 kcal/mol. Among them, five compounds, namely Michellamine B, Quercetin 3-O-(2'',6''-digalloyl)-beta-D-galactopyranoside, Corilagin, Hypericin, and 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose residues, bound effi-ciently with the binding site of RdRp. Besides, Lopinavir, Maraviroc, and Remdesivir drugs also inhibited SARS-CoV-2 polymerase. In addition, the ADMET properties of top potential compounds were also predicted in comparison to the drugs. Conclusion: The present study suggested that these potential drug candidates can be further subjected to in vitro and in vivo studies that may help develop effective anti-COVID-19 drugs.