A novel robust inhibitor of papain-like protease (PLpro) as a COVID-19 drug.

Regarding the significance of SARS-CoV-2, scientists have shown considerable interest in developing effective drugs. Inhibitors for PLpro are the primary strategies for locating suitable COVID-19 drugs. Natural compounds comprise the majority of COVID-19 drugs. Due to limitations on the safety of clinical trials in cases of COVID, computational methods are typically utilized for inhibition studies. Whereas papain is highly similar to PLpro and is entirely safe, the current study aimed to examine several plant secondary metabolites to identify the most effective papain inhibitor and validate the results using molecular dynamics and docking. This simulation was conducted identically for PLpro and the optimal inhibitor. The results indicated that the experimental results are comparable to those obtained In-Silico, and the inhibition effects of Chlorogenic acid (CGA) on papain attained in the experiment were validated (IC=0.54 mM). CGA as an inhibitor was located in the active site of PLpro and papain (total energy -2009410 and -456069 kJ/mol, respectively) at the desired location and distance. The study revealed that CGA and its derivatives are effective PLpro inhibitors against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.