In Vitro Evaluation of In Silico Screening Approaches in Search for Selective ACE2 Binding Chemical Probes

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...

Full description

Saved in:
Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2022-08, Vol.27 (17), p.5400
Main 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
Format: Article
Language:English
Subjects:
ACE2
Angiotensin converting enzyme
Angiotensin-converting enzyme 2
Binding
Binding sites
blood-brain barrier penetration
Chemical Sciences
Cheminformatics
Drug discovery
Enzymes
Enzymology
Health aspects
Investigations
Ligands
Medicinal Chemistry
Methods
molecular docking
Neprilysin
Nervous system diseases
Neurological diseases
Optimization
Physiological aspects
Probes
Protein binding
Proteins
QSAR modeling
selective ACE2 enzyme binding
Selectivity
Severe acute respiratory syndrome coronavirus 2
Structure-activity relationships
Tissues
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27175400