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- Title
In Vitro Evaluation of In Silico Screening Approaches in Search for Selective ACE2 Binding Chemical Probes.
- Authors
Rayevsky, Alexey V.; Poturai, Andrii S.; Kravets, Iryna O.; Pashenko, Alexander E.; Borisova, Tatiana A.; Tolstanova, Ganna M.; Volochnyuk, Dmitriy M.; Borysko, Petro O.; Vadzyuk, Olga B.; Alieksieieva, Diana O.; Zabolotna, Yuliana; Klimchuk, Olga; Horvath, Dragos; Marcou, Gilles; Ryabukhin, Sergey V.; Varnek, Alexandre
- Abstract
New models for ACE2 receptor binding, based on QSAR and docking algorithms were developed, using XRD structural data and ChEMBL 26 database hits as training sets. The selectivity of the potential ACE2-binding ligands towards Neprilysin (NEP) and ACE was evaluated. The Enamine screening collection (3.2 million compounds) was virtually screened according to the above models, in order to find possible ACE2-chemical probes, useful for the study of SARS-CoV2-induced neurological disorders. An enzymology inhibition assay for ACE2 was optimized, and the combined diversified set of predicted selective ACE2-binding molecules from QSAR modeling, docking, and ultrafast docking was screened in vitro. The in vitro hits included two novel chemotypes suitable for further optimization.
- Subjects
ANGIOTENSIN converting enzyme; MEDICAL screening; NEPRILYSIN; QSAR models; ENZYMOLOGY
- Publication
Molecules, 2022, Vol 27, Issue 17, p5400
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules27175400