Prediction of the small molecule selectivity index against influenza virus strain A/H1N1 using machine learning methods

Russian Chemical Bulletin, Journal Year: 2025, Volume and Issue: 74(3), P. 851 - 864

Published: March 1, 2025

Language: Английский

Consensus Pharmacophore Strategy For Identifying Novel SARS-Cov-2 M^pro Inhibitors from Large Chemical Libraries

Journal of Chemical Information and Modeling, Journal Year: 2024, Volume and Issue: 64(6), P. 1984 - 1995

Published: March 12, 2024

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main Protease (Mpro) is an enzyme that cleaves viral polyproteins translated from the genome and critical for replication. Mpro a target anti-SARS-CoV-2 drug development, multiple crystals complexed with competitive inhibitors have been reported. In this study, we aimed to develop consensus pharmacophore as tool expand search inhibitors. We generated model by aligning summarizing pharmacophoric points 152 bioactive conformers of SARS-CoV-2 Validation against library subset ligands showed our retrieved poses reproduced crystal-binding mode in 77% cases. Using models derived pharmacophore, screened >340 million compounds. Pharmacophore-matching chemoinformatics analyses identified new potential candidate compounds were chemically dissimilar reference set, among them, demonstrating relevance model. evaluated effect 16 candidates on enzymatic activity finding seven inhibitory activity. Three (1, 4, 5) had IC50 values midmicromolar range. reported herein can be used identify improved novel chemical scaffolds Mpro. method developed its generation provided open-access code (https://github.com/AngelRuizMoreno/ConcensusPharmacophore) applied other pharmacological targets.

Language: Английский

Natural Product Databases for Drug Discovery: Features and Applications

Pharmaceutical Science Advances, Journal Year: 2024, Volume and Issue: 2, P. 100050 - 100050

Published: Aug. 24, 2024

Language: Английский