Identification of potential binders of the main protease 3CLpro of the COVID-19 via structure-based ligand design and molecular modeling

• DOI: 10.1016/j.cplett.2020.137489
• Publication Date: 2020-04-18T03:08:10Z
• Authors: Marina Macchiagodena; Marco Pagliai; Piero Procacci
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3CL-PRO; 3CL-PRO inhibitor; Binding affinity; Coronavirus; Coronavirus main protease; COVID-19; Molecular docking; Molecular dynamics; SARS-CoV2; General Physics and Astronomy; Physical and Theoretical Chemistry; Article; 3. Good health

We have applied a computational strategy, using a combination of virtual screening, docking and molecular dynamics techniques, aimed at identifying possible lead compounds for the non-covalent inhibition of the main protease 3CLpro of the SARS-CoV2 Coronavirus. Based on the X-ray structure (PDB code: 6LU7), ligands were generated using a multimodal structure-based design and then docked to the monomer in the active state. Docking calculations show that ligand-binding is strikingly similar in SARS-CoV and SARS-CoV2 main proteases. The most potent docked ligands are found to share a common binding pattern with aromatic moieties connected by rotatable bonds in a pseudo-linear arrangement.