Identification of Inhibitors of SARS-CoV-2 3CL-Pro Enzymatic Activity Using a Small Molecule in Vitro Repurposing Screen.


Journal

ACS pharmacology & translational science
ISSN: 2575-9108
Titre abrégé: ACS Pharmacol Transl Sci
Pays: United States
ID NLM: 101721411

Informations de publication

Date de publication:
11 Jun 2021
Historique:
received: 17 12 2020
entrez: 15 3 2022
pubmed: 16 3 2022
medline: 16 3 2022
Statut: epublish

Résumé

Compound repurposing is an important strategy for the identification of effective treatment options against SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (3CL-Pro), also termed M-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyproteins pp1a and pp1ab at multiple distinct cleavage sites. We here report the results of a repurposing program involving 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and small molecules regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro and have identified 62 additional compounds with IC

Identifiants

pubmed: 35287429
doi: 10.1021/acsptsci.0c00216
pmc: PMC7986981
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1096-1110

Informations de copyright

© 2021 The Authors. Published by American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

Références

Eur J Med Chem. 2020 Nov 15;206:112702
pubmed: 32798789
Nat Commun. 2020 Jun 24;11(1):3202
pubmed: 32581217
Assay Drug Dev Technol. 2011 Apr;9(2):165-73
pubmed: 21133675
Nature. 2020 Sep;585(7824):293-297
pubmed: 32494016
J Biomol Struct Dyn. 2021 Jun;39(9):3099-3114
pubmed: 32329408
Nat Med. 2017 Apr 7;23(4):405-408
pubmed: 28388612
Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14
pubmed: 23793146
N Engl J Med. 2020 Nov 5;383(19):1813-1826
pubmed: 32445440
Int J Antimicrob Agents. 2020 Sep;56(3):106078
pubmed: 32629115
J Biol Chem. 2020 Dec 11;295(50):17365-17373
pubmed: 33060199
Int J Mol Sci. 2020 Jul 28;21(15):
pubmed: 32731361
RSC Med Chem. 2020 Dec 21;12(3):370-379
pubmed: 34041486
Structure. 2020 Dec 1;28(12):1313-1320.e3
pubmed: 33152262
Nat Commun. 2020 Sep 4;11(1):4417
pubmed: 32887884
Antiviral Res. 2018 Oct;158:199-205
pubmed: 30138642
N Engl J Med. 2021 Feb 25;384(8):693-704
pubmed: 32678530
FEBS J. 2014 Sep;281(18):4085-96
pubmed: 25039866
Acta Pharm Sin B. 2020 May;10(5):766-788
pubmed: 32292689
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42
pubmed: 21460441
PLoS Pathog. 2016 Mar 30;12(3):e1005531
pubmed: 27027316
FEBS Lett. 2007 Nov 27;581(28):5454-8
pubmed: 17981158
J Chem Inf Model. 2013 Jun 24;53(6):1518-27
pubmed: 23617275
J Nat Prod. 2016 Mar 25;79(3):616-28
pubmed: 26900761
J Virol Methods. 2005 Oct;129(1):56-63
pubmed: 15961169
Cell Res. 2020 Aug;30(8):678-692
pubmed: 32541865
J Chem Inf Model. 2013 Jun 24;53(6):1503-17
pubmed: 23590204
Perspect Drug Discov Des. 1996;6(1):64-86
pubmed: 32288276
Nat Rev Drug Discov. 2016 May;15(5):327-47
pubmed: 26868298
Antiviral Res. 2015 Mar;115:21-38
pubmed: 25554382
Sci Rep. 2018 Feb 15;8(1):3102
pubmed: 29449607
iScience. 2021 Oct 22;24(10):103213
pubmed: 34632326
Acta Pharmacol Sin. 2020 Sep;41(9):1167-1177
pubmed: 32737471
J Med Chem. 2004 Mar 25;47(7):1739-49
pubmed: 15027865
J Med Chem. 2022 Feb 24;65(4):2716-2746
pubmed: 33186044
J Chem Inf Model. 2011 Mar 28;51(3):578-96
pubmed: 21323318
FEBS Lett. 2009 Feb 4;583(3):549-55
pubmed: 19166843
J Enzyme Inhib Med Chem. 2020 Dec;35(1):1539-1544
pubmed: 32746637
ACS Pharmacol Transl Sci. 2021 Mar 16;4(3):1079-1095
pubmed: 34136757
Chem Biol. 2011 Nov 23;18(11):1401-12
pubmed: 22118674
Mikrobiol Zh (1978). 1979 Jan-Feb;41(1):69-74
pubmed: 440154
Sci Data. 2021 Feb 26;8(1):70
pubmed: 33637768
Oxid Med Cell Longev. 2009 Nov-Dec;2(5):270-8
pubmed: 20716914
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
J Biomol Screen. 2006 Apr;11(3):247-52
pubmed: 16490779
Science. 2020 Apr 24;368(6489):409-412
pubmed: 32198291
ACS Pharmacol Transl Sci. 2020 Sep 04;3(5):1008-1016
pubmed: 33062953
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Int J Mol Sci. 2020 May 20;21(10):
pubmed: 32443911
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877
pubmed: 31588918
JAMA. 2020 Apr 21;323(15):1488-1494
pubmed: 32125362
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
J Virol. 2012 Sep;86(18):10112-22
pubmed: 22787216
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Biochem Soc Trans. 2011 Oct;39(5):1371-5
pubmed: 21936817

Auteurs

Maria Kuzikov (M)

Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany.

Elisa Costanzi (E)

Elettra-Sincrotrone Trieste S.C.p.A., SS 14 - km 163, 5 in AREA Science Park, 34149 Basovizza, Trieste, Italy.

Jeanette Reinshagen (J)

Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany.

Francesca Esposito (F)

Dipartimento di Scienze della vita e dell'ambiente, Cittadella Universitaria di Monserrato, SS-554 Monserrato, Cagliari, Italy.

Laura Vangeel (L)

Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Herestraat 49, Box 1043, 3000 Leuven, Belgium.

Markus Wolf (M)

Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany.

Bernhard Ellinger (B)

Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany.

Carsten Claussen (C)

Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany.

Gerd Geisslinger (G)

Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor Stern Kai 7, 60596 Frankfurt am Main, Germany.
Institute of Clinical Pharmacology, Goethe-University, Theodor Stern Kai 7, 60590 Frankfurt, Germany.

Angela Corona (A)

Dipartimento di Scienze della vita e dell'ambiente, Cittadella Universitaria di Monserrato, SS-554 Monserrato, Cagliari, Italy.

Daniela Iaconis (D)

Dompé Farmaceutici SpA, via Campo di Pile, 67100 L'Aquila, Italy.

Carmine Talarico (C)

Dompé Farmaceutici SpA, via Campo di Pile, 67100 L'Aquila, Italy.

Candida Manelfi (C)

Dompé Farmaceutici SpA, via Campo di Pile, 67100 L'Aquila, Italy.

Rolando Cannalire (R)

Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131 Naples, Italy.

Giulia Rossetti (G)

Institute of Neuroscience and Medicine (INM-9)/Institute for Advanced Simulation (IAS-5) and Jülich Supercomputing Centre (JSC) Forschungszentrum Jülich, D-52425 Jülich, Germany.
Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany.

Jonas Gossen (J)

Institute of Neuroscience and Medicine (INM-9)/Institute for Advanced Simulation (IAS-5) and Jülich Supercomputing Centre (JSC) Forschungszentrum Jülich, D-52425 Jülich, Germany.

Simone Albani (S)

Institute of Neuroscience and Medicine (INM-9)/Institute for Advanced Simulation (IAS-5) and Jülich Supercomputing Centre (JSC) Forschungszentrum Jülich, D-52425 Jülich, Germany.

Francesco Musiani (F)

Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, 40216 Bologna, Italy.

Katja Herzog (K)

EU-OPENSCREEN ERIC, Robert-Rössle-Straße 10, 13125 Berlin, Germany.

Yang Ye (Y)

University of Chinese Academy of Sciences, Beijing 100049, China.

Barbara Giabbai (B)

Elettra-Sincrotrone Trieste S.C.p.A., SS 14 - km 163, 5 in AREA Science Park, 34149 Basovizza, Trieste, Italy.

Nicola Demitri (N)

Elettra-Sincrotrone Trieste S.C.p.A., SS 14 - km 163, 5 in AREA Science Park, 34149 Basovizza, Trieste, Italy.

Dirk Jochmans (D)

Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Herestraat 49, Box 1043, 3000 Leuven, Belgium.

Steven De Jonghe (S)

Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Herestraat 49, Box 1043, 3000 Leuven, Belgium.

Jasper Rymenants (J)

Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Herestraat 49, Box 1043, 3000 Leuven, Belgium.

Vincenzo Summa (V)

Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131 Naples, Italy.

Enzo Tramontano (E)

Dipartimento di Scienze della vita e dell'ambiente, Cittadella Universitaria di Monserrato, SS-554 Monserrato, Cagliari, Italy.

Andrea R Beccari (AR)

Dompé Farmaceutici SpA, via Campo di Pile, 67100 L'Aquila, Italy.

Pieter Leyssen (P)

Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Herestraat 49, Box 1043, 3000 Leuven, Belgium.

Paola Storici (P)

Elettra-Sincrotrone Trieste S.C.p.A., SS 14 - km 163, 5 in AREA Science Park, 34149 Basovizza, Trieste, Italy.

Johan Neyts (J)

Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Herestraat 49, Box 1043, 3000 Leuven, Belgium.

Philip Gribbon (P)

Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany.

Andrea Zaliani (A)

Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, 22525 Hamburg, Germany.

Classifications MeSH