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Structure Elucidation of Coxsackievirus A16 in Complex with GPP3 Informs a Systematic Review of Highly Potent Capsid Binders to Enteroviruses

DOI: 10.1371/journal.ppat.1005165 DOI Help
PMID: 26485389 PMID Help

Authors: Luigi De Colibus (University of Oxford) , Xiangxi Wang (Chinese Academy of Science) , Aloys Tijsma (Rega Institute for Medical Research) , Johan Neyts (Rega Institute for Medical Research) , John Spyrou (University of Oxford) , Jingshan Ren (University of Oxford) , Jonathan Grimes (Division of Structural Biology, University of Oxford) , Gerhard Puerstinger (University of Innsbruck) , Pieter Leyssen (Rega Institute for Medical Research) , Liz Fry (University of Oxford) , Zihe Rao (Tsinghua University) , Dave Stuart (Diamond Light Source) , Richard J. Kuhn
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Plos Pathogens , VOL 11 (10)

State: Published (Approved)
Published: October 2015

Open Access Open Access

Abstract: The replication of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), which are the major cause of hand, foot and mouth disease (HFMD) in children, can be inhibited by the capsid binder GPP3. Here, we present the crystal structure of CVA16 in complex with GPP3, which clarifies the role of the key residues involved in interactions with the inhibitor. Based on this model, in silico docking was performed to investigate the interactions with the two next-generation capsid binders NLD and ALD, which we show to be potent inhibitors of a panel of enteroviruses with potentially interesting pharmacological properties. A meta-analysis was performed using the available structural information to obtain a deeper insight into those structural features required for capsid binders to interact effectively and also those that confer broad-spectrum anti-enterovirus activity.

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography