The in silico prediction of hotspot residues that contribute to the structural stability of subunit interfaces of a picornavirus capsid

Upfold, N. , Ross, C., Bishop, Ö. T. and Knox, C. (2020) The in silico prediction of hotspot residues that contribute to the structural stability of subunit interfaces of a picornavirus capsid. Viruses, 12(4), 387. (doi: 10.3390/v12040387) (PMID:32244486) (PMCID:PMC7232237)

Abstract

The assembly of picornavirus capsids proceeds through the stepwise oligomerization of capsid protein subunits and depends on interactions between critical residues known as hotspots. Few studies have described the identification of hotspot residues at the protein subunit interfaces of the picornavirus capsid, some of which could represent novel drug targets. Using a combination of accessible web servers for hotspot prediction, we performed a comprehensive bioinformatic analysis of the hotspot residues at the intraprotomer, interprotomer and interpentamer interfaces of the Theiler’s murine encephalomyelitis virus (TMEV) capsid. Significantly, many of the predicted hotspot residues were found to be conserved in representative viruses from different genera, suggesting that the molecular determinants of capsid assembly are conserved across the family. The analysis presented here can be applied to any icosahedral structure and provides a platform for in vitro mutagenesis studies to further investigate the significance of these hotspots in critical stages of the virus life cycle with a view to identify potential targets for antiviral drug design.

• Item Type: Articles
• Additional Information: This research was supported by Medical Research Council (MRC, South Africa) and Research Council (RC, Rhodes University) grants awarded to CK. OTB thanks the National Research Foundation of South Africa (grant number 93690). NU was supported by postgraduate fellowships from the NRF and the German Academic Exchange Service (DAAD). CR was supported through the Rhodes University Henderson scholarship program.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Upfold, Dr Nicole
• Authors: Upfold, N., Ross, C., Bishop, Ö. T., and Knox, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Viruses
• Publisher: MDPI
• ISSN: 1999-4915
• ISSN (Online): 1999-4915
• Published Online: 31 March 2020
• Copyright Holders: Copyright © 2020 by the authors.
• First Published: First published in Viruses 12(4):387
• Publisher Policy: Reproduced under a Creative Commons license