The impact of curcumin derived polyphenols on the structure and flexibility COVID-19 main protease binding pocket: a molecular dynamics simulation study

PeerJ. 2021 Jul 19:9:e11590. doi: 10.7717/peerj.11590. eCollection 2021.

Abstract

The newly occurred SARS-CoV-2 caused a leading pandemic of coronavirus disease (COVID-19). Up to now it has infected more than one hundred sixty million and killed more than three million people according to 14 May 2021 World Health Organization report. So far, different types of studies have been conducted to develop an anti-viral drug for COVID-19 with no success yet. As part of this, silico were studied to discover and introduce COVID-19 antiviral drugs and results showed that protease inhibitors could be very effective in controlling. This study aims to investigate the binding affinity of three curcumin derived polyphenols against COVID-19 the main protease (Mpro), binding pocket, and identification of important residues for interaction. In this study, molecular modeling, auto-dock coupled with molecular dynamics simulations were performed to analyze the conformational, and stability of COVID-19 binding pocket with diferuloylmethane, demethoxycurcumin, and bisdemethoxycurcumin. All three compounds have shown binding affinity -39, -89 and -169.7, respectively. Demethoxycurcumin and bisdemethoxycurcumin showed an optimum binding affinity with target molecule and these could be one of potential ligands for COVID-19 therapy. And also, COVID-19 main protease binding pocket binds with the interface region by one hydrogen bond. Moreover, the MD simulation parameters indicated that demethoxycurcumin and bisdemethoxycurcumin were stable during the simulation run. These findings can be used as a baseline to develop therapeutics with curcumin derived polyphenols against COVID-19.

Keywords: Binding energy; Docking; NAMD; SARS-CoV-2; X-ray crustal structure.

Grants and funding

This work was supported by the University of Addis Ababa Science and Technology for using computational resources. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.