Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
17 09 2021
Historique:
received: 28 02 2021
accepted: 30 08 2021
entrez: 18 9 2021
pubmed: 19 9 2021
medline: 30 9 2021
Statut: epublish

Résumé

Novel coronavirus disease 2019 (COVID-19) has emerged as a global pandemic with far-reaching societal impact. Here we demonstrate that Pin1 is a key cellular molecule necessary for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) propagation. In this study, siRNA-mediated silencing of Pin1 expression markedly suppressed the proliferation of SARS-CoV-2 in VeroE6/TMPRSS2 cells. In addition, several recently generated Pin1 inhibitors showed strong inhibitory effects on SARS-CoV-2 proliferation, measured by both viral mRNA and protein synthesis, and alleviated the cytopathic effect (CPE) on VeroE6/TMPRSS2 cells. One compound, termed H-77, was found to block SARS-CoV-2 proliferation at an EC

Identifiants

pubmed: 34535740
doi: 10.1038/s41598-021-97972-3
pii: 10.1038/s41598-021-97972-3
pmc: PMC8448864
doi:

Substances chimiques

NIMA-Interacting Peptidylprolyl Isomerase 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

18581

Subventions

Organisme : Japan Society for the Promotion of Science
ID : Grant-in-Aid for Scientific Research (C)
Organisme : Japan Society for the Promotion of Science
ID : Grant-in-Aid for Scientific Research (C)
Organisme : Japan Society for the Promotion of Science
ID : Grant-in-Aid for Scientific Research (B)
Organisme : Japan Agency for Medical Research and Development
ID : Development of Technology to Control Viral Infections
Organisme : Hiroshima Prefecture, Japan
ID : Goverment-Academia Collaboration

Informations de copyright

© 2021. The Author(s).

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Auteurs

Takeshi Yamamotoya (T)

Department of Medical Chemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Yusuke Nakatsu (Y)

Department of Medical Chemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Machi Kanna (M)

Department of Medical Chemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Shun Hasei (S)

Department of Medical Chemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Yukino Ohata (Y)

Department of Medical Chemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Jeffrey Encinas (J)

Anenti Therapeutics Japan, Inc., 4-3 Yamaashiya-cho, Ashiya, 659-0082, Japan.

Hisanaka Ito (H)

School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.

Takayoshi Okabe (T)

Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Tomoichiro Asano (T)

Department of Medical Chemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. tasano@hiroshima-u.ac.jp.

Takemasa Sakaguchi (T)

Department of Virology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. tsaka@hiroshima-u.ac.jp.

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Classifications MeSH