tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2020 Nov 12;1-27.
doi: 10.1080/22221751.2020.1850183. Online ahead of print.
Human coronavirus dependency on host heat shock protein 90 reveals an antiviral target
Cun Li[SUP] 1 2 [/SUP], Hin Chu[SUP] 1 2 [/SUP], Xiaojuan Liu[SUP] 2 [/SUP], Man Chun Chiu[SUP] 2 [/SUP], Xiaoyu Zhao[SUP] 2 [/SUP], Dong Wang[SUP] 2 [/SUP], Yuxuan Wei[SUP] 2 [/SUP], Yuxin Hou[SUP] 2 [/SUP], Huiping Shuai[SUP] 2 [/SUP], Jianpiao Cai[SUP] 2 [/SUP], Jasper Fuk-Woo Chan[SUP] 1 2 3 [/SUP], Jie Zhou[SUP] 1 2 [/SUP], Kwok Yung Yuen[SUP] 1 2 3 [/SUP]
Affiliations
Abstract
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.
Keywords: Hsp90β; SARS-CoV-2; coronavirus; nucleoprotein; viral replication.
. 2020 Nov 12;1-27.
doi: 10.1080/22221751.2020.1850183. Online ahead of print.
Human coronavirus dependency on host heat shock protein 90 reveals an antiviral target
Cun Li[SUP] 1 2 [/SUP], Hin Chu[SUP] 1 2 [/SUP], Xiaojuan Liu[SUP] 2 [/SUP], Man Chun Chiu[SUP] 2 [/SUP], Xiaoyu Zhao[SUP] 2 [/SUP], Dong Wang[SUP] 2 [/SUP], Yuxuan Wei[SUP] 2 [/SUP], Yuxin Hou[SUP] 2 [/SUP], Huiping Shuai[SUP] 2 [/SUP], Jianpiao Cai[SUP] 2 [/SUP], Jasper Fuk-Woo Chan[SUP] 1 2 3 [/SUP], Jie Zhou[SUP] 1 2 [/SUP], Kwok Yung Yuen[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 33179566
- DOI: 10.1080/22221751.2020.1850183
Abstract
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.
Keywords: Hsp90β; SARS-CoV-2; coronavirus; nucleoprotein; viral replication.