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

Autor: Rayevsky AV; Enamine Ltd., 78 Chervonotkatska Street, 02660 Kyiv, Ukraine.; Institute of Food Biotechnology and Genomics, National Academy of Sciences of Ukraine, 2a Osipovskogo Street, 04123 Kyiv, Ukraine., Poturai AS; Enamine Ltd., 78 Chervonotkatska Street, 02660 Kyiv, Ukraine., Kravets IO; Enamine Ltd., 78 Chervonotkatska Street, 02660 Kyiv, Ukraine.; Chemspace LLC, 85 Chervonotkatska Street, 02094 Kyiv, Ukraine., Pashenko AE; Enamine Ltd., 78 Chervonotkatska Street, 02660 Kyiv, Ukraine.; Educational and Scientific Institute of High Technologies, Taras Shevchenko National University of Kyiv, 60 Volodymyrska Street, 01033 Kyiv, Ukraine.; Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 5 Murmanska Street, 03028 Kyiv, Ukraine., Borisova TA; Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 9 Leontovitcha Street, 01054 Kyiv, Ukraine., Tolstanova GM; Educational and Scientific Institute of High Technologies, Taras Shevchenko National University of Kyiv, 60 Volodymyrska Street, 01033 Kyiv, Ukraine., Volochnyuk DM; Enamine Ltd., 78 Chervonotkatska Street, 02660 Kyiv, Ukraine.; Chemspace LLC, 85 Chervonotkatska Street, 02094 Kyiv, Ukraine.; Educational and Scientific Institute of High Technologies, Taras Shevchenko National University of Kyiv, 60 Volodymyrska Street, 01033 Kyiv, Ukraine., Borysko PO; Enamine Ltd., 78 Chervonotkatska Street, 02660 Kyiv, Ukraine., Vadzyuk OB; Enamine Ltd., 78 Chervonotkatska Street, 02660 Kyiv, Ukraine., Alieksieieva DO; Enamine Ltd., 78 Chervonotkatska Street, 02660 Kyiv, Ukraine., Zabolotna Y; Laboratory of Chemoinformatics, University of Strasbourg, 4, rue B. Pascal, 67081 Strasbourg, France., Klimchuk O; Laboratory of Chemoinformatics, University of Strasbourg, 4, rue B. Pascal, 67081 Strasbourg, France., Horvath D; Laboratory of Chemoinformatics, University of Strasbourg, 4, rue B. Pascal, 67081 Strasbourg, France., Marcou G; Laboratory of Chemoinformatics, University of Strasbourg, 4, rue B. Pascal, 67081 Strasbourg, France., Ryabukhin SV; Enamine Ltd., 78 Chervonotkatska Street, 02660 Kyiv, Ukraine.; Educational and Scientific Institute of High Technologies, Taras Shevchenko National University of Kyiv, 60 Volodymyrska Street, 01033 Kyiv, Ukraine.; Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 5 Murmanska Street, 03028 Kyiv, Ukraine., Varnek A; Laboratory of Chemoinformatics, University of Strasbourg, 4, rue B. Pascal, 67081 Strasbourg, France.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2022 Aug 24; Vol. 27 (17). Date of Electronic Publication: 2022 Aug 24.
DOI: 10.3390/molecules27175400
Abstrakt: 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.
Databáze: MEDLINE
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