Developments towards antiviral therapies against enterovirus 71

Abstract

Enterovirus 71 (EV71) has emerged as a clinically important neurotropic virus that can cause acute flaccid paralysis and encephalitis, leading to cardiopulmonary failure and death. Recurring outbreaks of EV71 have been reported in several countries. The current lack of approved anti-EV71 therapy has prompted intense research into antiviral development. Several strategies--ranging from target-based chemical design to compound library screenings--have been employed, while others revisited compound series generated from antiviral developments against poliovirus and human rhinoviruses. These efforts have given rise to a diversity of antiviral candidates that include small molecules and non-conventional nucleic-acid-based strategies. This review aims to highlight candidates with potential for further clinical development based on their putative modes of action.

Figure 1

Graphical overview of picornavirus replication. Virus particle first attaches to host cell surface via a cellular receptor before entering and uncoating to unveil the viral RNA genome. Viral RNA is translated by cellular translational machinery to give a polyprotein that is then cleaved by the virus-encoded proteases 2A^pro and 3C^pro to give functional precursor proteins (e.g. 2BC and 3CD) and individual proteins. Within virus-induced membrane vesicles, viral RNA (+) is copied by the viral RNA polymerase, 3D^pol, to give (−) strand RNA intermediates, which in turn provide the template for the synthesis of (+) strand viral RNA. The (+) strand viral RNAs are used to generate more (−) strand viral RNAs, translated into viral proteins or packaged into progeny virions. Lysis of host cells will result in the release of progeny virions. Adapted and modified from Figure 2 in Ref. and Figure 4 In Ref. .