Human coronavirus dependency on host heat shock protein 90 reveals an antiviral target.
Emerg Microbes Infect
; 9(1): 2663-2672, 2020 Dec.
Article
in English
| MEDLINE | ID: covidwho-919316
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 Hsp90ß, but not Hsp90α, significantly restricted MERS-CoV replication and abolished virus spread. Third, Hsp90ß interaction with MERS-CoV nucleoprotein (NP) was revealed in a co-immunoprecipitation assay. Hsp90ß 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
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Benzoquinones
/
HSP90 Heat-Shock Proteins
/
Lactams, Macrocyclic
/
Middle East Respiratory Syndrome Coronavirus
/
Host Microbial Interactions
Limits:
Animals
/
Humans
Language:
English
Journal:
Emerg Microbes Infect
Year:
2020
Document Type:
Article
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