A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infection
Infection with coxsackievirus A10 (CV-A10) can cause hand-foot-mouth disease and is also associated with severe complications, including viral pneumonia, aseptic and viral meningitis. Coxsackievirus infection may also play a role in the pathogenesis of acute myocardial infarction and in the increase...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-01-01
|
| Series: | Current Research in Microbial Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S266651742300024X |
| _version_ | 1827591071991857152 |
|---|---|
| author | Yongkang Chen Xiaohong Li Min Wang Yuan Li Jun Fan Jingjing Yan Shuye Zhang Lu Lu Peng Zou |
| author_facet | Yongkang Chen Xiaohong Li Min Wang Yuan Li Jun Fan Jingjing Yan Shuye Zhang Lu Lu Peng Zou |
| author_sort | Yongkang Chen |
| collection | DOAJ |
| description | Infection with coxsackievirus A10 (CV-A10) can cause hand-foot-mouth disease and is also associated with severe complications, including viral pneumonia, aseptic and viral meningitis. Coxsackievirus infection may also play a role in the pathogenesis of acute myocardial infarction and in the increased risk of type 1 diabetes mellitus in adults. However, there are no approved vaccines or direct antiviral agents available to prevention or treatment of coxsackievirus infection. Here, we reported that GC376 potently inhibited CV-A10 infection in different cell lines without cytotoxicity, significantly suppressed production of viral proteins, and strongly reduced the yields of infectious progeny virions. Further study indicated that GC376, as viral 3C protease inhibitor, had the potential to restrain the cleavage of the viral polyprotein into individually functional proteins, thus suppressed the replication of CV-A10. Furthermore, the drug exhibited antiviral activity against coxsackieviruses of various serotypes including CV-A6, CV-A7 and CV-A16, suggesting that GC376 is a broad-spectrum anti-coxsackievirus inhibitor and the 3C protease is a promising target for developing anti-coxsackievirus agents. |
| first_indexed | 2024-03-09T01:26:38Z |
| format | Article |
| id | doaj.art-b7462f50ed5f4bd79935c058e7f30ce4 |
| institution | Directory Open Access Journal |
| issn | 2666-5174 |
| language | English |
| last_indexed | 2024-03-09T01:26:38Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Microbial Sciences |
| spelling | doaj.art-b7462f50ed5f4bd79935c058e7f30ce42023-12-10T06:18:13ZengElsevierCurrent Research in Microbial Sciences2666-51742023-01-015100203A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infectionYongkang Chen0Xiaohong Li1Min Wang2Yuan Li3Jun Fan4Jingjing Yan5Shuye Zhang6Lu Lu7Peng Zou8Shanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaShanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaShanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaShanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaShanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaShanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaClinical Center for BioTherapy and Institutes of Biomedical Sciences, Zhongshan Hospital, Fudan University, Shanghai, China; Corresponding authors.Shanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China; Corresponding authors.Shanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China; Corresponding authors.Infection with coxsackievirus A10 (CV-A10) can cause hand-foot-mouth disease and is also associated with severe complications, including viral pneumonia, aseptic and viral meningitis. Coxsackievirus infection may also play a role in the pathogenesis of acute myocardial infarction and in the increased risk of type 1 diabetes mellitus in adults. However, there are no approved vaccines or direct antiviral agents available to prevention or treatment of coxsackievirus infection. Here, we reported that GC376 potently inhibited CV-A10 infection in different cell lines without cytotoxicity, significantly suppressed production of viral proteins, and strongly reduced the yields of infectious progeny virions. Further study indicated that GC376, as viral 3C protease inhibitor, had the potential to restrain the cleavage of the viral polyprotein into individually functional proteins, thus suppressed the replication of CV-A10. Furthermore, the drug exhibited antiviral activity against coxsackieviruses of various serotypes including CV-A6, CV-A7 and CV-A16, suggesting that GC376 is a broad-spectrum anti-coxsackievirus inhibitor and the 3C protease is a promising target for developing anti-coxsackievirus agents.http://www.sciencedirect.com/science/article/pii/S266651742300024XCoxsackievirusCysteine protease3C proteaseProtease inhibitorAntiviralGC376 |
| spellingShingle | Yongkang Chen Xiaohong Li Min Wang Yuan Li Jun Fan Jingjing Yan Shuye Zhang Lu Lu Peng Zou A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infection Current Research in Microbial Sciences Coxsackievirus Cysteine protease 3C protease Protease inhibitor Antiviral GC376 |
| title | A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infection |
| title_full | A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infection |
| title_fullStr | A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infection |
| title_full_unstemmed | A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infection |
| title_short | A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infection |
| title_sort | cysteine protease inhibitor gc376 displays potent antiviral activity against coxsackievirus infection |
| topic | Coxsackievirus Cysteine protease 3C protease Protease inhibitor Antiviral GC376 |
| url | http://www.sciencedirect.com/science/article/pii/S266651742300024X |
| work_keys_str_mv | AT yongkangchen acysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT xiaohongli acysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT minwang acysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT yuanli acysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT junfan acysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT jingjingyan acysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT shuyezhang acysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT lulu acysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT pengzou acysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT yongkangchen cysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT xiaohongli cysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT minwang cysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT yuanli cysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT junfan cysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT jingjingyan cysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT shuyezhang cysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT lulu cysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection AT pengzou cysteineproteaseinhibitorgc376displayspotentantiviralactivityagainstcoxsackievirusinfection |