In silico Molecular Docking of SARS-CoV-2 Surface Proteins with Benzimidazole Scaffolds: Strategy to Discover Lead Compounds

Abstract

The severe acute respiratory illness that was brought on because of the outbreak of COVID-19 caused by the SARS-CoV-2 infection has been designated as a public health emergency of worldwide concern. There is an immediate and pressing need to establish an effective therapeutic strategy to bring infections under control. COVID-19 viral spike glycoproteins and proteases both play important roles in the process of viral entrance as well as in the process of virus reproduction. Benzimidazole derivatives show antiviral activity against various RNA and DNA viruses and stop the early viral replication cycle. Based on this information, we designed eighteen new benzimidazole derivatives and screened them against the proteins S-glycoprotein 6VSB and papain-like protease 6W9C using molecular docking studies. Compounds that bind strongly to these proteins were evaluated again in an in vitro study. When docked with SARS-CoV-2 spike glycoprotein, the binding affinity of R1 and R7 was –7.1 kcal/mol and -7.3 kcal/mol, respectively. This showed that they might be able to stop the SARS spike protein from binding to the ACE2 receptor on the human host, making it harder for the virus to get into the cells. The binding affinity of SARS-CoV-2 papain-like protease with R4, R14, and R15 was –6.7 kcal/mol, -6.5 kcal/mol, and –6.5 kcal/mol, respectively. COVID-19 could stop the protease from working by binding it. It was suggested, on the basis of the binding energy score, that these pharmacologically potent benzimidazole derivatives may be tested against SARS-CoV-2 and utilized in the production of efficient antiviral medicines