Structure-based Molecular Docking in the Identification of Novel Inhibitors Targeting SARS-CoV-2 Main Protease

Abstract

There have been several studies of natural compounds used as SARS-CoV-2 inhibitors. Among those, we selected the most viable natural anti-viral compound, rutin, as a basis for structure-based molecular docking campaign using databases of commercially available compounds that are potential ligands. The known and well-studied SARS-CoV-2 main protease structure was used as a target and Asinex screening library was filtered to select structurally similar and pharmacokinetically feasible compounds. Before screening campaing, the protein was minimized and selected compounds were protonated and parametrized. A modified version of rDock high-throughput virtual screening tool called RxDock was used for molecular docking. RxDock was developed to enable running large molecular docking studes on modern computer systems, including supercomputers and clouds. Our approach combines traditional approach of pharmaceutical industry where natural compounds are used as a template to develop novel inhibitors while using novel high-throughput virtual screening techniques and validation tests. It promises to pave a way to develop an agnostic approach in development of novel inhibitors while keeping the cost of both the computational protocols and bioassays lower than the current drug discovery pipeline.