How to deal with future possible coronavirus: hints from the analysis of the interaction between potential inhibitors with 3C-Like protease via molecular docking

The COVID-19 pandemic has resulted in millions of infections and deaths. However, there is still a lack of broad-spectrum effective and safe anti-CoV drugs. 3CL protease is one of the promising targets for the development of anti-CoV drugs. In this study, we explored the binding effects of 36 potential inhibitors with five hu-man coronavirus 3CL proteases (SARS-CoV-2, MERS-CoV, SARS-CoV, HCoV-HKU1 and HCoV-229E) via molecular docking using SwissDock. The correlation study demonstrated that small molecule inhibitors with higher molecular weight were likely to be more effective. Based on the fact that SARS-CoV-2 3CLpro had the poorest binding tendency and affinity with ligands, we predicted that the CoVs will become more and more difficult to overcome as they evolve. The interaction analysis showed that the lethal human coronavirus 3CL proteases had higher hydrogen bonding interaction propensity on Glu16X. These findings offer interesting perspectives for future drug design strategies against human coronavirus.