Biophysical Society Thematic Meeting - November 16-20, 2015

Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Speaker Abstracts

In Silico Analysis of Evolutionary Conserved Interacting Motifs within Picornavirus Capsids Caroline Ross , Caroline Knox, Özlem Tastan Bishop. Rhodes University, Grahamstown, South Africa. The Picornaviridae family contains a number of pathogens with economic and clinical importance. Recent reports have indicated the emergence of novel picornaviruses associated with gastrointestinal, neurological and respiratory diseases in humans. Currently there are no antivirals available for the treatment of picornavirus infections and the application of effective vaccines has only been successful for certain viruses. Picornavirus capsids are icosahedral, comprising of 60 protomer structures each assembled through the interaction of four subunit proteins: VP1, VP2, VP3 and VP4. However, the protein-protein interactions that facilitate protomer assembly are poorly understood. An investigation into the role of conserved individual subunit residues in such interactions will broaden the understanding of picornavirus evolution as well as provide guidelines for the development of antiviral therapeutics. This study provides a comprehensive examination of the capsid phylogenies, with a novel comparative analysis of amino acid motifs and interactions conserved across the viral family, viral genera and picornaviruses of the same host species. The functions of conserved motifs were deduced by the in silico prediction of interacting residues within the crystal structures with subsequent structural analysis, of representative protomers of enteroviruses, Foot-and-Mouth-Disease-Virus and Theiler’s Virus. Findings in this study suggest that the capsid proteins might be evolving independently from the replication proteins through possible inter-typic recombination of functional protein regions. Additionally the study predicts that protomer assembly is facilitated through a network of multiple subunit-subunit interactions. Specifically, 30 interacting motifs were predicted to contain residues involved in interprotein interactions. The study identified 50 interacting residues conserved across the enterovirus capsids, with 26 universally conserved residue-residue interactions and 43 interactions sustained through conservative site mutations. The presented results may serve as fundamental guidelines for the development of economically feasible antivirals specifically targeting virus assembly.

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