Delavirdine and Dolutegravir as Potential Inhibitors of SARSCoV-2 Main Protease (Mpro): An In-Silico Study

ABSTRACT

SARS-CoV-2 is a recently discovered member of coronaviruses (CoVs) family that is very contagious and has a high infectivity rate. Expanding the search for antivirals which act against SARS-CoV-2 would allow more treatment options for infected patients, accelerate their recovery time, and avoid some serious adverse effects that the limited number of approved medications might cause. In this study, we assess 74 antiviral agents, chloroquine, and hydroxychloroquine inhibitory activity against the virus's main protease (Mpro), which is essential for its replication. Virtual screening of the compounds has been conducted where the screened ligands were assessed according to their binding energy to the main binding pocket of Mpro. Ten antivirals, in addition to chloroquine and hydroxychloroquine were further studied through molecular docking simulations and assessed for their binding conformations and interactions with the protein's catalytic dyad residues. Furthermore, molecular dynamics simulations were established to study delavirdine, dolutegravir, raltegravir and vicriviroc for 100 ns. Results show that delavirdine and dolutegravir are excellent candidates that can inhibit the catalytic activity of Mpro. This could significantly reduce patients' hospitalisation time and the need for secondary measures. © 2022 Jordan Journal of Biological Sciences. All rights reserved