3.9 Article

2C protein of Enterovirus: key protein of viral replication and antiviral target

Journal

VIROLOGIE
Volume 27, Issue 3, Pages 35-49

Publisher

JOHN LIBBEY EUROTEXT LTD
DOI: 10.1684/vir.2023.1002

Keywords

Enterovirus; protein 2C; inhibitors; antivirals

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This review provides an overview of the current research status on the 2C protein as an antiviral target, as well as the mode of action of specific inhibitors targeting this protein.
Enteroviruses (EVs) include many human pathogens of increasing public health concern. These EVs are often associated with mild clinical manifestations, but they can lead to serious complications such as encephalitis, meningitis, pneumonia, myocarditis or poliomyelitis. Despite significant advances, there is no approved antiviral therapy for the treatment of enterovirus infections. Due to the high genotypic diversity of EVs, molecules targeting highly conserved viral proteins may be considered for developing a pan-EV treatment. In this regard, the ATPase/Helicase 2C, which is a highly conserved non-structural protein among EVs, has essential functions for viral replication and is therefore an attractive antiviral target. Recent functional and structural studies on the 2C protein led to the identification of molecules showing ex vivo anti-EV activity and associated with resistance mutations on the coding sequence of the 2C protein. This review presents the current state of knowledge about the 2C protein from an antiviral target perspective and the mode of action of specific inhibitors for this therapeutic target.

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