2C protein of Enterovirus: key protein of viral replication and antiviral target Volume 27, issue 3, Mai-Juin 2023


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1 AFMB, CNRS UMR 7257, Aix-Marseille Université, Case 925, 163 av. de Luminy, 13288 Marseille cedex 09, France
2 Unité des Virus émergents (UVE), Aix-Marseille Université, IRD 190,Inserm 1207, Marseille, France
3 Laboratory of Applied Biotechnology (LBA3B), Azm Center for Research in Biotechnology and its Applications, EDST, Lebanese University, Tripoli 1300, Lebanon
4 Department of Biology, Faculty of Sciences 3, Lebanese University, Michel Slayman Tripoli Campus Ras Maska, Tripoli 1352, Lebanon
5 Aix-Marseille Université, CNRS, Institut de Chimie radicalaire (ICR) UMR7273, Équipe Pharmaco-chimie radicalaire, Faculté de Pharmacie, 27 bld Jean Moulin, CS30064, 13385 Marseille cedex 05, France
* Correspondance : K. Barral
# The authors contributed equally.

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.