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

Abstract

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 (IC₅₀=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

Keywords:

• SARS-CoV-2
• Chlorogenic acid
• molecular dynamics
• papain
• PLpro

Disclosure statement

The authors do not have any financial and personal relationships with other people or organization(s) that could directly or indirectly affect or bias this research. No conflict of interest exists in the submission of this manuscript, and the manuscript was approved by all the authors for publication.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.