Studying the limits of protein-ligand docking to predict new non-covalent inhibitors for the SARSCoV-2 main protease

Identifier:  TDX:4141

Handle: https://hdl.handle.net/20.500.11797/TDX4141

Authors:  Macip Sancho, Guillem

Abstract:
The global pandemic known as COVID-19 (COronaVIrus Disease 2019) had a profound impact on healthcare systems around the world, straining countries and societies in ways not seen since globalization. SARS-CoV-2, a positive sense single-stranded RNA virus from the Betacoronavirus genus, is the causative agent of COVID-19, and it has been thoroughly investigated by the scientific community since December 2019. The SARS-CoV-2 main protease (M-pro) is one of the more frequently investigated viral targets. Our research group devised a virtual screening methodology based on protein-ligand docking during the start of the COVID-19 pandemic to identify new SARS-CoV-2 M-pro inhibitors among approved drugs. When we compared our results to those of other suggested SARS-CoV-2 M-pro inhibitors, we discovered that numerous articles predicted different compounds, albeit utilizing the same starting dataset and approach. In a short period of time, there were a large number of proposed M-pro inhibitors and structures of non-covalent complexes between SARS-CoV-2 M-pro, which supplied the breeding ground for this thesis. The current PhD thesis examines in depth the limitations of protein-ligand docking in predicting SARS-CoV-2 M-pro inhibitors.