Emerging Microbes and Infections (Jan 2020)

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

  • Cun Li,
  • Hin Chu,
  • Xiaojuan Liu,
  • Man Chun Chiu,
  • Xiaoyu Zhao,
  • Dong Wang,
  • Yuxuan Wei,
  • Yuxin Hou,
  • Huiping Shuai,
  • Jianpiao Cai,
  • Jasper Fuk-Woo Chan,
  • Jie Zhou,
  • Kwok Yung Yuen

DOI
https://doi.org/10.1080/22221751.2020.1850183
Journal volume & issue
Vol. 9, no. 1
pp. 2663 – 2672

Abstract

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ABSTRACTRapid 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.

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