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

被引：1

作者：

Rayevsky, Alexey, V ^{[1
,2
]}

Poturai, Andrii S. ^{[1
]}

Kravets, Iryna O. ^{[1
,3
]}

Pashenko, Alexander E. ^{[1
,4
,5
]}

Borisova, Tatiana A. ^{[6
]}

Tolstanova, Ganna M. ^{[4
]}

Volochnyuk, Dmitriy M. ^{[1
,3
,4
]}

Borysko, Petro O. ^{[1
]}

Vadzyuk, Olga B. ^{[1
]}

Alieksieieva, Diana O. ^{[1
]}

Zabolotna, Yuliana ^{[7
]}

Klimchuk, Olga ^{[7
]}

Horvath, Dragos ^{[7
]}

Marcou, Gilles ^{[7
]}

Ryabukhin, Sergey, V ^{[1
,4
,5
]}

Varnek, Alexandre ^{[7
]}

机构：

[1] Enamine Ltd, 78 Chervonotkatska St, UA-02660 Kiev, Ukraine

[2] Natl Acad Sci Ukraine, Inst Food Biotechnol & Genom, 2a Osipovskogo St, UA-04123 Kiev, Ukraine

[3] Chemspace LLC, 85 Chervonotkatska St, UA-02094 Kiev, Ukraine

[4] Taras Shevchenko Natl Univ Kyiv, Educ & Sci Inst High Technol, 60 Volodymyrska St, UA-01033 Kiev, Ukraine

[5] Natl Acad Sci Ukraine, Inst Organ Chem, 5 Murmanska St, UA-03028 Kiev, Ukraine

[6] Natl Acad Sci Ukraine, Palladin Inst Biochem, 9 Leontovitcha St, UA-01054 Kiev, Ukraine

[7] Univ Strasbourg, Lab Chemoinformat, 4 Rue B Pascal, F-67081 Strasbourg, France

来源：

MOLECULES | 2022年 / 27卷 / 17期

基金：

新加坡国家研究基金会;

关键词：

QSAR modeling; molecular docking; Neprilysin; angiotensin-converting enzyme; selective ACE2 enzyme binding; blood-brain barrier penetration; enzymology inhibition assay adjustment; in vitro studies; DOCKING; ICM; ARCHITECTURE; INHIBITORS; PLATFORM; DESIGN; POTENT; DOMAIN;

D O I：

10.3390/molecules27175400

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：18

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