Simeprevir Potently Suppresses SARS-CoV-2 Replication and Synergizes with Remdesivir.


Journal

ACS central science
ISSN: 2374-7943
Titre abrégé: ACS Cent Sci
Pays: United States
ID NLM: 101660035

Informations de publication

Date de publication:
26 May 2021
Historique:
received: 03 09 2020
entrez: 2 6 2021
pubmed: 3 6 2021
medline: 3 6 2021
Statut: ppublish

Résumé

The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global threat to human health. Using a multidisciplinary approach, we identified and validated the hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. Simeprevir potently reduces SARS-CoV-2 viral load by multiple orders of magnitude and synergizes with remdesivir

Identifiants

pubmed: 34075346
doi: 10.1021/acscentsci.0c01186
pmc: PMC8056950
doi:

Types de publication

Journal Article

Langues

eng

Pagination

792-802

Subventions

Organisme : NIAID NIH HHS
ID : HHSN272201400006C
Pays : United States

Informations de copyright

© 2021 The Authors. Published by American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare the following competing financial interest(s): CUHK and HKU have filed a US provisional patent application based on the finding of this manuscript. W.L.N., M.C.W.C., K.P.Y.H., H.S.L., K.S.K., H.K., and H.-M.L. are inventors of the patent. F.K.L.C. has served as a consultant to Eisai, Pfizer, Takeda, and Otsuka and has been paid lecture fees by Eisai, Pfizer, AstraZeneca, and Takeda.

Références

Sci Rep. 2018 Jan 19;8(1):1230
pubmed: 29352168
BJGP Open. 2020 Jun 23;4(2):
pubmed: 32265182
Cell Res. 2020 Mar;30(3):269-271
pubmed: 32020029
Lancet. 2020 May 16;395(10236):1569-1578
pubmed: 32423584
Open Forum Infect Dis. 2020 Apr 15;7(4):ofaa130
pubmed: 32363212
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Lancet. 2020 Feb 15;395(10223):497-506
pubmed: 31986264
Antimicrob Agents Chemother. 2009 Apr;53(4):1377-85
pubmed: 19171797
Bioinformatics. 2005 Aug 15;21(16):3439-40
pubmed: 16082012
Lancet Respir Med. 2020 Jul;8(7):687-695
pubmed: 32386571
J Virol. 2020 Oct 14;94(21):
pubmed: 32817221
Nat Commun. 2020 Sep 17;11(1):4682
pubmed: 32943628
N Engl J Med. 2020 May 7;382(19):1787-1799
pubmed: 32187464
Antiviral Res. 2020 Jun;178:104786
pubmed: 32251767
Nature. 2021 Apr;592(7852):116-121
pubmed: 33106671
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
J Med Chem. 2014 Mar 13;57(5):1673-93
pubmed: 24446688
Heart Rhythm. 2020 Sep;17(9):1425-1433
pubmed: 32407884
Cell Res. 2020 Aug;30(8):678-692
pubmed: 32541865
N Engl J Med. 2020 Apr 30;382(18):1708-1720
pubmed: 32109013
Lancet. 2020 Mar 28;395(10229):1054-1062
pubmed: 32171076
Mol Cell. 2020 Sep 3;79(5):710-727
pubmed: 32853546
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nat Rev Drug Discov. 2016 May;15(5):327-47
pubmed: 26868298
J Virol. 2005 Mar;79(6):3846-50
pubmed: 15731278
J Med Virol. 2021 Mar;93(3):1403-1408
pubmed: 32767684
Science. 2020 May 1;368(6490):489-493
pubmed: 32179701
Nat Med. 2008 Jul;14(7):762-6
pubmed: 18552857
Nature. 2020 Nov;587(7835):657-662
pubmed: 32726803
Sci Transl Med. 2011 Jul 13;3(91):91ra63
pubmed: 21753122
Sci Transl Med. 2020 Apr 29;12(541):
pubmed: 32253226
Cell. 2021 Jan 7;184(1):76-91.e13
pubmed: 33147444
JAMA. 2020 Jun 23;323(24):2493-2502
pubmed: 32392282
Clin Pharmacol Ther. 2016 Feb;99(2):224-34
pubmed: 26259716
Sci Rep. 2020 Aug 17;10(1):13866
pubmed: 32807895
J Comput Chem. 2010 Jan 30;31(2):455-61
pubmed: 19499576
J Virol Methods. 2021 Feb;288:114013
pubmed: 33166547
Proc Natl Acad Sci U S A. 2021 Feb 2;118(5):
pubmed: 33452205
Cell Host Microbe. 2020 Jun 10;27(6):870-878
pubmed: 32464097
Science. 2020 Apr 24;368(6489):409-412
pubmed: 32198291
J Infect Dis. 2011 Dec 15;204(12):1866-78
pubmed: 22013225
Science. 2020 May 15;368(6492):779-782
pubmed: 32277040
Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):E1012-E1021
pubmed: 29339515
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
PLoS One. 2010 Oct 06;5(10):e13197
pubmed: 20949131
N Engl J Med. 2020 Jun 18;382(25):2411-2418
pubmed: 32379955
Science. 2020 Jun 26;368(6498):1499-1504
pubmed: 32358203
Cell Rep. 2021 May 18;35(7):109133
pubmed: 33984267
Viruses. 2020 Apr 14;12(4):
pubmed: 32295237
Nat Struct Mol Biol. 2020 Jun;27(6):529-532
pubmed: 32382072
J Chem Inf Model. 2015 Nov 23;55(11):2324-37
pubmed: 26479676
Nature. 2020 Jun;582(7811):289-293
pubmed: 32272481
Life Sci. 2020 Oct 1;258:118205
pubmed: 32777300
Mol Cell. 2016 Apr 7;62(1):121-36
pubmed: 26949039
JAMA. 2020 May 12;323(18):1824-1836
pubmed: 32282022
Cell. 2020 May 28;181(5):1036-1045.e9
pubmed: 32416070
Lancet. 2020 Feb 15;395(10223):507-513
pubmed: 32007143
Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):E3900-9
pubmed: 25197083
J Biol Chem. 2020 May 15;295(20):6785-6797
pubmed: 32284326
J Transl Med. 2020 Apr 22;18(1):179
pubmed: 32321524
BMJ. 2020 Dec 16;371:m4857
pubmed: 33328153
Nature. 2020 Oct;586(7827):113-119
pubmed: 32707573
J Biomol Struct Dyn. 2020 Sep 2;:1-12
pubmed: 32873185
Eur J Med Chem. 2013 Jan;59:1-6
pubmed: 23202846

Auteurs

Ho Sing Lo (HS)

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Kenrie Pui Yan Hui (KPY)

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong.
Centre for Immunology and Infection (C2I), Hong Kong Science Park, Hong Kong, SAR, China.

Hei-Ming Lai (HM)

Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Xu He (X)

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Khadija Shahed Khan (KS)

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Simranjeet Kaur (S)

Department of Chemistry, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong.

Junzhe Huang (J)

Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Zhongqi Li (Z)

Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Anthony K N Chan (AKN)

Department of Systems Biology, Beckman Research Institute, City of Hope, Duarte, California 91010, United States.

Hayley Hei-Yin Cheung (HH)

School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong.

Ka-Chun Ng (KC)

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong.

John Chi Wang Ho (JCW)

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong.

Yu Wai Chen (YW)

Department of Applied Biology and Chemical Technology and the State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom, Hong Kong.

Bowen Ma (B)

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Peter Man-Hin Cheung (PM)

School of Public Health, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Donghyuk Shin (D)

Buchmann Institute for Molecular Life Sciences, Goethe University, 60323 Frankfurt am Main, Germany.
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.

Kaidao Wang (K)

Protein Production Department, GenScript Biotech Corporation, Nanjing, Jiangsu Province 211100, China.

Meng-Hsuan Lee (MH)

Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan 115.

Barbara Selisko (B)

Laboratoire d'Architecture et Fonction des Macromolécules Biologiques (AFMB), Centre National de la Recherche Scientifique, Aix-Marseille Université, 13007 Marseille, France.

Cecilia Eydoux (C)

Laboratoire d'Architecture et Fonction des Macromolécules Biologiques (AFMB), Centre National de la Recherche Scientifique, Aix-Marseille Université, 13007 Marseille, France.

Jean-Claude Guillemot (JC)

Laboratoire d'Architecture et Fonction des Macromolécules Biologiques (AFMB), Centre National de la Recherche Scientifique, Aix-Marseille Université, 13007 Marseille, France.

Bruno Canard (B)

Laboratoire d'Architecture et Fonction des Macromolécules Biologiques (AFMB), Centre National de la Recherche Scientifique, Aix-Marseille Université, 13007 Marseille, France.

Kuen-Phon Wu (KP)

Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan 115.

Po-Huang Liang (PH)

Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan 115.

Ivan Dikic (I)

Buchmann Institute for Molecular Life Sciences, Goethe University, 60323 Frankfurt am Main, Germany.

Zhong Zuo (Z)

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Francis K L Chan (FKL)

Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

David S C Hui (DSC)

Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Stanley Ho Center for Emerging Infectious Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Vincent C T Mok (VCT)

Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Gerald Choa Neuroscience Centre, Margaret K. L. Cheung Research Centre for Management of Parkinsonism, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Kam-Bo Wong (KB)

School of Life Sciences, Centre for Protein Science and Crystallography, State Key Laboratory of Agrobiotechnology, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong.

Chris Ka Pun Mok (CKP)

HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Shatin, Hong Kong.

Ho Ko (H)

Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Gerald Choa Neuroscience Centre, Margaret K. L. Cheung Research Centre for Management of Parkinsonism, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Peter Hung Pain Research Institute, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Wei Shen Aik (WS)

Department of Chemistry, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong.

Michael Chi Wai Chan (MCW)

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong.
Centre for Immunology and Infection (C2I), Hong Kong Science Park, Hong Kong, SAR, China.

Wai-Lung Ng (WL)

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Classifications MeSH