In silico drug repurposing for coronavirus (COVID-19): screening known HCV drugs against the SARS-CoV-2 spike protein bound to angiotensin-converting enzyme 2 (ACE2) (6M0J)

In this study, FDA-approved HCV antiviral drugs and their structural analogues—several of them in clinical trials—were tested for their inhibitory properties toward the SARS-CoV-2 spike protein bound to angiotensin-converting enzyme 2 (6M0J) using a virtual screening approach and computational chemistry methods. The most stable structures and the corresponding binding affinities of thirteen such antiviral compounds were obtained. Frontier molecular orbital theory, global reactivity descriptors, molecular docking calculations and electrostatic potential analysis were used to hypothesize the bioactivity of these drugs against 6M0J. It is found that an increased affinity for the protein is shown by inhibitors with large compound volume, relatively higher electrophilicity index, aromatic rings and heteroatoms that participate in hydrogen bonding. Among the tested drugs, four compounds 10–13 showed excellent results—binding affinities − 11.2 to − 11.5 kcal mol(−1). These four top scoring compounds may act as lead compounds for further experimental validation, clinical trials and even for the development of more potent antiviral agents against the SARS-CoV-2. GRAPHICAL ABSTRACT: Approved HCV drugs and analogues were tested for their bioactivity towards the SARS-CoV-2 (6M0J) using virtual screening, ESP and MD analysis. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11030-022-10469-7.