Homology Modeling of Coronavirus Structural Proteins and Molecular Docking of Potential Drug Candidates for the Treatment of COVID-19

ABSTRACT

Background: The discovery of a novel strain of coronavirus in 2019 (COVID-19) has triggered a series of tragic events in the world with thousands of deaths recorded daily. Despite the huge resources committed to the discovery of vaccines against this highly pathogenic virus, scientists are still unable to find suitable treatments for the disease. Understanding the structure of coronavirus proteins could provide a basis for the development of cheap, potent and, less toxic vaccines. Objective(s) This study was therefore designed to model coronavirus spike (S) glycoprotein and envelope (E) protein as well as to carry out molecular docking of potential drugs to the homologs and coronavirus main protease (Mpro). Method(s) Homology modeling of coronavirus spike (S) glycoprotein and envelope (E) protein was car-ried out using sequence deposited in the Uniprot database. The topological features of the model's catalytic site were evaluated using the CASTp server. Compounds reported as potential drugs against COVID-19 were docked to S glycoprotein, E protein, and coronavirus main protease (Mpro) to determine the best ligands and the mode of interaction. Result(s) Homology modeling of the proteins revealed structures with 91-98% sequence similarity with PDB entries. The catalytic site of the modeled proteins contained conserved residue involved in ligand binding. In addition, remdesivir, lopinavir, and ritonavir have a high binding affinity for the three proteins studied interacting with key residues in the protein's catalytic domain. Conclusion(s) Results from the study revealed that remdesivir, lopinavir, and ritonavir are inhibitors of key coronavirus proteins and therefore qualify for further studies as a potential treatment for coronavi-rus.Copyright © 2021 Bentham Science Publishers.