Ensemble docking based virtual screening of SARS-CoV-2 main protease inhibitors.
Mol Inform
; : e202300279, 2024 Jul 08.
Article
em En
| MEDLINE
| ID: mdl-38973780
ABSTRACT
During the first years of COVID-19 pandemic, X-ray structures of the coronavirus drug targets were acquired at an unprecedented rate, giving hundreds of PDB depositions in less than a year. The main protease (Mpro) of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is the primary validated target of direct-acting antivirals. The selection of the optimal ensemble of structures of Mpro for the docking-driven virtual screening campaign was thus non-trivial and required a systematic and automated approach. Here we report a semi-automated active site RMSD based procedure of ensemble selection from the SARS-CoV-2 Mpro crystallographic data and virtual screening of its inhibitors. The procedure was compared with other approaches to ensemble selection and validated with the help of hand-picked and peer-reviewed activity-annotated libraries. Prospective virtual screening of non-covalent Mpro inhibitors resulted in a new chemotype of thienopyrimidinone derivatives with experimentally confirmed enzyme inhibition.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Mol Inform
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Federação Russa