Human coronavirus dependency on host heat shock protein 90 reveals an antiviral target. Issue 1 (1st January 2020)

• Record Type: Journal Article
• Authors: Li, Cun; Chu, Hin; Liu, Xiaojuan; Chiu, Man Chun; Zhao, Xiaoyu; Wang, Dong; Wei, Yuxuan; Hou, Yuxin; Shuai, Huiping; Cai, Jianpiao; Chan, Jasper Fuk-Woo; Zhou, Jie; Yuen, Kwok Yung
• Is Part Of: Emerging microbes & infections. Volume 9:Issue 1(2020)
• Page Start: 2663
• Page End: 2672
• Publication Date: 2020-01-01
• Subjects: Coronavirus -- Hsp90β -- SARS-CoV-2 -- nucleoprotein -- viral replication; Medical microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.9041
• DOI: 10.1080/22221751.2020.1850183
• Languages: English
• ISSNs: 2222-1751

Abstract

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.