<i>In Silico</i> Evaluation for the Inhibitory Action of Curcumin Derivatives on the SARS-CoV-2 Proteins

Abstract

Purpose of the Study: COVID-19 is caused by the SARS-CoV-2 virus that had a global pandemic spread in the last two years. Symptoms of the disease include respiratory distress and, in severe cases may consequently lead to death. Blocking the viral proteins can aid in treating this disease and alleviating its symptoms. Two target proteins of the coronavirus that are hot spots in drug discovery are the papain-like protease PL-pro and the main protease M-pro. PL-pro is an enzyme that is required for processing viral polyproteins to generate a functional replicase complex and enable viral spread. M-pro is the major protease of SARS-CoV-2, which is a keystone in viral replication and transcription. Methods: In this study, we shed the light on the route of targeting viral proteins for disease alleviation, by targeting the two aforementioned enzymes, PL-pro and M-pro using in silico studies. Docking experiments, using AutoDock algorithms, were performed to predict the inhibitory effect of recently produced synthetic derivatives of curcumin on the viral proteins. Results: Most of the curcumin derivatives have shown variable levels of inhibition, e.g., S1 - S6, mainly on the papain-like protease, and to a lesser extent on the main protease. Conclusion: The results indicated that curcumin derivatives can be potent anti-viral drug of SARS-CoV-2, namely targeting the papain-like protease.