Lopinavir and Ritonavir have a high affinity to SARS-CoV-2 S-protein Receptor-Binding Domain sequenced in Brazil

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected at China in December 2019 and rapid worldwide spread, causing the coronavirus disease 2019 (COVID-19). In this pandemic situation, the importance of structural-functional relationships between virus and host cell should be considered. In this work, we investigated the molecular interactions of seven drugs used in clinical therapy by in silico analysis with specific protein target of SARS-CoV-2 – RBD domain of the Brazilian S protein genome sequence – in docking models. Initially, a three-dimensional structure of SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) model was obtained by homology. Then, a prediction analysis of cavities in the RBD structure was performed to detect a possible active site in the S protein fragment. Our molecular docking study demonstrated that only 2 ligands showed considerably acceptable values in relation to the seven drugs (Umifenovir, Darunavir, Lopinavir, Ritonavir, Remdesivir, Pirfenidone, Oseltamivir) used to screen. The interaction between Lopinavir and RBD revealed binding affinity of -9.8 kcal/mol and interactions with residues PHE168, GLY167, SER176, GLN175, GLU166, LEU134, LEU137, TYR171, PHE138, LEU174, PHE172. Ritonavir demonstrated binding affinity of -8.9 kcal/mol and interactions with residues ARG148, ASN130, VAL23, SER81, ASN33, PHE29, TYR33, SER31, ASN132, ALA26, ALA30, ALA34, TYR133. Molecular dynamics simulations were performed to evaluate the stability of the complexes formed. The present study shows that protease inhibitors Lopinavir and Ritonavir have best binding at the active site (the RBD of S protein) through molecular docking.