Abstract
Seneca Valley virus (SVV) is a newly discovered picornavirus in the Senecavirus genus. SVV-001 strain has shown promise as an oncolytic virus against tumors with neuroendocrine features. There is a need to use a structurebased approach to develop virus-like particles capable to mimicking the architecture of naturally occurring empty capsids that can be used as vaccines or as carriers for targeted cancer treatment. However, these empty capsids are inherently less stable, and tedious to purify. This warrants investigation into factors which confer the SVV capsid stability and into combining this knowledge to recombinantly express stable SVV VLPs. In this study, we isolated a thermostable mutant of SVV by thermal selection assays and we characterized a single mutation located in a capsid protein. The cryo-EM map of this mutant showed conformational shifts that facilitated the formation of additional hydrogen bonds and aromatic interactions, which could serve as capsid stabilizing factors.