The structure of enterovirus 71 and its implications for the design of capsid binding anti-viral compounds

Pavel Plevka1, Rushika Perera1, Jane Cardosa2, Richard J. Kuhn1, and
Michael G. Rossmann1

 

1 Department of Biological Sciences, Purdue University, 240 S. Martin Jischke Drive, West Lafayette, Indiana 47907-2032, USA

2Sentinext Therapeutics, 19H Menara Northam, 55 Jalan Sultan Ahmad Shah, 10050 Penang, Malaysia

Enterovirus 71 is a picornavirus associated with fatal neurological illness in infants and young children. Stability of most picornaviruses is regulated by a pocket factor, a lipid molecule, located within a pocket of one of the capsid proteins. Binding of an immunoglobulin-like receptor molecule into the canyon, a depression on capsid surface, induces release of the pocket factor, resulting in particle destabilization and genome release. Nevertheless, the two EV71 receptors that have been identified do not belong to the immunoglobulin family. Here we report that EV71 retains the pocket factor suggesting that the destabilization of particles is regulated by its expulsion. Unlike in other picornaviruses, the pocket factor of EV71 is partly exposed on the canyon floor and interacts with polar residues. Thus the structure of anti-EV71 compounds will need to include a hydrophilic head group designed to interact with residues at the entrance of the pocket.