Multi-Phase In Silico Discovery of Potential SARS-CoV-2 RNA-Dependent RNA Polymerase Inhibitors among 3009 Clinical and FDA-Approved Related Drugs

Abstract

Proceeding our prior studies of SARS-CoV-2, the inhibitory potential against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) has been investigated for a collection of 3009 clinical and FDA-approved drugs. A multi-phase in silico approach has been employed in this study. Initially, a molecular fingerprint experiment of Remdesivir (RTP), the co-crystallized ligand of the examined protein, revealed the most similar 150 compounds. Among them, 30 compounds were selected after a structure similarity experiment. Subsequently, the most similar 30 compounds were docked against SARS-CoV-2 RNA-dependent RNA polymerase (PDB ID: 7BV2). Aloin 359, Baicalin 456, Cefadroxil 1273, Sophoricoside 1459, Hyperoside 2109, and Vitexin 2286 exhibited the most precise binding modes, as well as the best binding energies. To confirm the obtained results, MD simulations experiments have been conducted for Hyperoside 2109, the natural flavonoid glycoside that exhibited the best docking scores, against RdRp (PDB ID: 7BV2) for 100 ns. The achieved results authenticated the correct binding of 2109, showing low energy and optimum dynamics. Our team presents these outcomes for scientists all over the world to advance in vitro and in vivo examinations against COVID-19 for the promising compounds.