Using Point Arrays to Characterize Drug-Bound Hepatitis B Virus and Human Enterovirus 71 Capsid Structures

Abstract

A virus capsid is composed of identical protein subunits which occupy chemically equivalent environments and assemble according to icosahedral symmetry. This protein shell holds critical roles throughout the viral life cycle including protecting the viral genome, facilitating binding to a host, and initiating viral replication. Because the capsid ultimately allows for infection, disrupting its symmetry has been identified as a promising strategy for antiviral treatments. This study focused on using point arrays to characterize the structural changes of drug-bound Hepatitis B Virus (HBV) and Human Enterovirus 71 (HEV-71) capsids. Point arrays represent the geometric constraints that icosahedral viruses conform to and provide insight into key protein associations and sites of stability at multiple radial levels. In this study, small molecule drugs intended to disrupt the capsid structure of HBV and compounds aimed to stabilize the structure of HEV-71 were analyzed. The results demonstrated that drug binding leads to a greater number of point array fits for the drugbound structures. The broad range of fits were consistent with the gauge point used to characterize the native capsids, yet also introduced new gauge point fits. These observations suggest that binding increases the conformational flexibility of the capsid as well as its stability. Additionally, the multiple fits proposed new locations of interest which may contribute to enhancing the stability of the capsid structure. Overall, point arrays were successfully fit to drug-bound virus capsids and these results demonstrate that point arrays are a valuable tool for assessing conformational changes caused by binding.