In Silico Evaluation of Potential SARS-CoV-2 RNA-Dependent RNA Polymerase (RdRp) Inhibitors Derived from Philippine Natural Products
TL;DR
Results suggest promising inhibitory capabilities of these three compounds against SARS-CoV-2 RdRp, and their shared presence in extracts of Vitex negundo, a Philippine medicinal plant, warrants further in vitro and in vivo investigation regarding the anti-SARS-CoV-2 activity of its extracts and active components.
Abstract
RNA-dependent RNA-polymerase (RdRp), one of the key enzymes in the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) life cycle, is a recognized druggable target for Coronavirus disease 19 (COVID-19) treatment. Its inhibition has been associated with reduced viral loads in infected individuals. A library of 1562 Philippine Natural Compounds was screened in silico for potential SARS-CoV-2 anti-RdRp activity using a high-throughput virtual screening (VS) approach. Molecular docking experiments and in silico absorption, distribution, metabolism, and excretion (ADME) predictions were used to determine compounds with potential inhibitory capabilities against RdRp. The top three compounds, Vitelignin A (VIT), Vitexoside (VIX), and Cannabifolin C (CAN), were subjected to molecular dynamics (MD) simulations in complex with RdRp, confirming the formation of stable protein-ligand complexes. Overall, these results suggest promising inhibitory capabilities of these three compounds against SARS-CoV-2 RdRp. Their shared presence in extracts of Vitex negundo, a Philippine medicinal plant, warrants further in vitro and in vivo investigation regarding the anti-SARS-CoV-2 activity of its extracts and active components.