Theoretical study on the interaction between candidate drugs and Coronavirus main protease (3CLPro) for inhibiting replication of SARS-CoV-2

Abstract

We theoretically investigated the interactions of drug molecules with 3C-like protease (3CLPro), to inhibit the replication of SARS-CoV-2 using molecular dynamics (MD) simulation. Lopinavir, Ritonavir, CG376 and dipeptidyl series were used at different temperatures and concentrations. The adsorption behavior of drug candidates was compared by analyzing the root mean square fluctuation (RMSF) of 3CLPro, minimum distances and interaction energies between 3CLPro and drug and radial distribution function(RDF). The drugs were mainly adsorbed on the 3CLpro by the polar interactions. In specifically, dipeptidyl 7a was effective in inhibiting 3CLPro since it shows high binding energy, high number of attached active sites 3CLPro and compared to those of dipeptidyl 6c. In specifically, alkyl groups within drugs mainly sticked to the active sites of 3CLPro. As higher concentration, the interactions between drugs and the protein were increased, which was shown by larger adsorption area of drugs on the protein, and however, average of interaction energy is lower. Meanwhile, the number of adsorbed drugs was similar in different temperature of the drugs