A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infection

Chen, Yongkang; Li, Xiaohong; Wang, Min; Li, Yuan; Fan, Jun; Yan, Jingjing; Zhang, Shuye; Lu, Lu; Zou, Peng

doi:10.1016/j.crmicr.2023.100203

Current Research in Microbial Sciences

2023

DOI: 10.1016/j.crmicr.2023.100203

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A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infection

Yongkang Chen,

Xiaohong Li,

Min Wang

et al.

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2024

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Cited by 4 publications

References 41 publications

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Integration of HiBiT into enteroviruses: A universal tool for advancing enterovirus virology research

Yu,

Li,

Zhang

et al. 2024

Virologica Sinica

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Integration of HiBiT into enteroviruses: A universal tool for advancing enterovirus virology research

Yu,

Li,

Zhang

et al. 2024

Virologica Sinica

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Non-Polio Enterovirus Inhibitors: Scaffolds, Targets, and Potency─What’s New?

Roux,

Touret,

Rathelot

et al. 2024

ACS Infect. Dis.

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The nucleoside analog 4′-fluorouridine suppresses the replication of multiple enteroviruses by targeting 3D polymerase

Chen,

Li,

Han

et al. 2024

Antimicrob Agents Chemother

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Human enteroviruses are the major pathogens causing hand-foot-and-mouth disease in infants and young children throughout the world, and infection with enterovirus is also associated with severe complications, such as aseptic meningitis and myocarditis. However, there are no antiviral drugs available to treat enteroviruses infection at present. In this study, we found that 4′-fluorouridine (4′-FlU), a nucleoside analog with low cytotoxicity, exhibited broad-spectrum activity against infections of multiple enteroviruses with EC50 values at low micromolar levels, including coxsackievirus A10 (CV-A10), CV-A16, CV-A6, CV-A7, CV-B3, enterovirus A71 (EV-A71), EV-A89, EV-D68, and echovirus 6. With further investigation, the results indicated that 4′-FlU directly interacted with the RNA-dependent RNA polymerase of enterovirus, the 3D pol , and impaired the polymerase activity of 3D pol , hence inhibiting viral RNA synthesis and significantly suppressing viral replication. Our ﬁndings suggest that 4′-FlU could be promisingly developed as a broad-spectrum direct-acting antiviral agent for anti-enteroviruses therapy.

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A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infection

Cited by 4 publications

References 41 publications

Integration of HiBiT into enteroviruses: A universal tool for advancing enterovirus virology research

Integration of HiBiT into enteroviruses: A universal tool for advancing enterovirus virology research

Non-Polio Enterovirus Inhibitors: Scaffolds, Targets, and Potency─What’s New?

The nucleoside analog 4′-fluorouridine suppresses the replication of multiple enteroviruses by targeting 3D polymerase

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