Article ; Online: Human coronavirus dependency on host heat shock protein 90 reveals an antiviral target.
Emerging microbes & infections
2020 Volume 9, Issue 1, Page(s) 2663–2672
Abstract: ... chaperones including heat shock protein 90 (Hsp90). Three highly pathogenic human coronaviruses, including ... 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. ...
| 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. |
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| MeSH term(s) | A549 Cells ; Animals ; Antiviral Agents/pharmacology ; Benzoquinones/pharmacology ; COVID-19/drug therapy ; Cell Line ; Chlorocebus aethiops ; HEK293 Cells ; HSP90 Heat-Shock Proteins/antagonists & inhibitors ; HSP90 Heat-Shock Proteins/genetics ; Host Microbial Interactions/drug effects ; Humans ; Intestines/virology ; Lactams, Macrocyclic/pharmacology ; Middle East Respiratory Syndrome Coronavirus/drug effects ; Organ Culture Techniques ; RNA, Small Interfering ; SARS Virus/drug effects ; SARS-CoV-2/drug effects ; Vero Cells ; Virus Replication/drug effects |
| Chemical Substances | Antiviral Agents ; Benzoquinones ; HSP90 Heat-Shock Proteins ; Lactams, Macrocyclic ; RNA, Small Interfering ; tanespimycin (4GY0AVT3L4) |
| Keywords | covid19 |
| Language | English |
| Publishing date | 2020-11-11 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2681359-2 |
| ISSN | 2222-1751 ; 2222-1751 |
| ISSN (online) | 2222-1751 |
| ISSN | 2222-1751 |
| DOI | 10.1080/22221751.2020.1850183 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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