Study of intermolecular interactions in diverse SARS-COV-2 MPRO inhibitors: what insights can we gain?

Identifier:  TFG:9371

Handle: https://hdl.handle.net/20.500.11797/TFG9371

Authors:  Trujillo de León, Said

Abstract:
The COVID-19 pandemic generated vast structural data on therapeutic targets, with SARS-CoV-2 main protease (MPRO) emerging as a key focus due to its role in viral replication and lack of human homologs. To support QSAR analysis, the open-source Python library CORAL-PIC was developed to detect non-covalent ligand–protein interactions. In a study of 378 MPRO–inhibitor complexes, CORAL-PIC condensed 300 MB of data into a 100 KB summary. Results revealed that hydrophobic and weak polar contacts dominate binding, while directional interactions with residues like CYS145 and GLY143 strongly correlate with activity. Key residues in the S1 subsite, such as GLU166 and MET165, were identified as conserved hotspots.