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Article: Human coronavirus dependency on host heat shock protein 90 reveals an antiviral target

TitleHuman coronavirus dependency on host heat shock protein 90 reveals an antiviral target
Authors
KeywordsSARS-CoV-2
nucleoprotein
Hsp90β
Coronavirus
viral replication
Issue Date2020
Citation
Emerging Microbes and Infections, 2020, v. 9, n. 1, p. 2663-2672 How to Cite?
Abstract© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. Rapid accumulation of viral proteins in host cells render viruses highly dependent on cellular chaperones including heat shock protein 90 (Hsp90). Three highly pathogenic human coronaviruses, including MERS-CoV, SARS-CoV and SARS-CoV-2, have emerged in the past 2 decades. However, there is no approved antiviral agent against these coronaviruses. We inspected the role of Hsp90 for coronavirus propagation. First, an Hsp90 inhibitor, 17-AAG, significantly suppressed MERS-CoV propagation in cell lines and physiological-relevant human intestinal organoids. Second, siRNA depletion of Hsp90β, but not Hsp90α, significantly restricted MERS-CoV replication and abolished virus spread. Third, Hsp90β interaction with MERS-CoV nucleoprotein (NP) was revealed in a co-immunoprecipitation assay. Hsp90β is required to maintain NP stability. Fourth, 17-AAG substantially inhibited the propagation of SARS-CoV and SARS-CoV-2. Collectively, Hsp90 is a host dependency factor for human coronavirus MERS-CoV, SARS-CoV and SARS-COV-2. Hsp90 inhibitors can be repurposed as a potent and broad-spectrum antiviral against human coronaviruses.
Persistent Identifierhttp://hdl.handle.net/10722/297314
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, Cun-
dc.contributor.authorChu, Hin-
dc.contributor.authorLiu, Xiaojuan-
dc.contributor.authorChiu, Man Chun-
dc.contributor.authorZhao, Xiaoyu-
dc.contributor.authorWang, Dong-
dc.contributor.authorWei, Yuxuan-
dc.contributor.authorHou, Yuxin-
dc.contributor.authorShuai, Huiping-
dc.contributor.authorCai, Jianpiao-
dc.contributor.authorChan, Jasper Fuk Woo-
dc.contributor.authorZhou, Jie-
dc.contributor.authorYuen, Kwok Yung-
dc.date.accessioned2021-03-15T07:33:30Z-
dc.date.available2021-03-15T07:33:30Z-
dc.date.issued2020-
dc.identifier.citationEmerging Microbes and Infections, 2020, v. 9, n. 1, p. 2663-2672-
dc.identifier.urihttp://hdl.handle.net/10722/297314-
dc.description.abstract© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. Rapid accumulation of viral proteins in host cells render viruses highly dependent on cellular chaperones including heat shock protein 90 (Hsp90). Three highly pathogenic human coronaviruses, including MERS-CoV, SARS-CoV and SARS-CoV-2, have emerged in the past 2 decades. However, there is no approved antiviral agent against these coronaviruses. We inspected the role of Hsp90 for coronavirus propagation. First, an Hsp90 inhibitor, 17-AAG, significantly suppressed MERS-CoV propagation in cell lines and physiological-relevant human intestinal organoids. Second, siRNA depletion of Hsp90β, but not Hsp90α, significantly restricted MERS-CoV replication and abolished virus spread. Third, Hsp90β interaction with MERS-CoV nucleoprotein (NP) was revealed in a co-immunoprecipitation assay. Hsp90β is required to maintain NP stability. Fourth, 17-AAG substantially inhibited the propagation of SARS-CoV and SARS-CoV-2. Collectively, Hsp90 is a host dependency factor for human coronavirus MERS-CoV, SARS-CoV and SARS-COV-2. Hsp90 inhibitors can be repurposed as a potent and broad-spectrum antiviral against human coronaviruses.-
dc.languageeng-
dc.relation.ispartofEmerging Microbes and Infections-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectSARS-CoV-2-
dc.subjectnucleoprotein-
dc.subjectHsp90β-
dc.subjectCoronavirus-
dc.subjectviral replication-
dc.titleHuman coronavirus dependency on host heat shock protein 90 reveals an antiviral target-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1080/22221751.2020.1850183-
dc.identifier.pmid33179566-
dc.identifier.pmcidPMC7751432-
dc.identifier.scopuseid_2-s2.0-85097660904-
dc.identifier.hkuros326110-
dc.identifier.volume9-
dc.identifier.issue1-
dc.identifier.spage2663-
dc.identifier.epage2672-
dc.identifier.eissn2222-1751-
dc.identifier.isiWOS:000599770500001-
dc.identifier.issnl2222-1751-

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