Recognition of Potential COVID-19 Drug Treatments through the Study of Existing Protein-Drug and Protein-Protein Structures: An Analysis of Kinetically Active Residues

Abstract

We report the results of our in silico study of approved drugs as potential treatments for COVID-19. The study is based on the analysis of normal modes of proteins. The drugs studied include chloroquine, ivermectin, remdesivir, sofosbuvir, boceprevir, and α-difluoromethylornithine (DMFO). We applied the tools we developed and standard tools used in the structural biology community. Our results indicate that small molecules selectively bind to stable, kinetically active residues and residues adjoining them on the surface of proteins and inside protein pockets, and that some prefer hydrophobic sites over other active sites. Our approach is not restricted to viruses and can facilitate rational drug design, as well as improve our understanding of molecular interactions, in general.

Keywords: COVID-19; boceprevir; chloroquine; ivermectin; normal-modes; proteins; protein–drug interactions; remdesivir; sofosbuvir; spike glycoprotein; α-difluoromethylornithine (DMFO).