Seneca Valley virus attachment and uncoating mediated by its receptor anthrax toxin receptor 1

Significance Seneca Valley virus (SVV) selectively infects and lyses neuroendocrine cancer cells, including small-cell lung cancer (SCLC) and pediatric neuroendocrine solid tumors, which are a major cause of morbidity and mortality. It is under development in clinical trials as an oncolytic agent against these tumors. Indeed preclinical and early-phase clinical trials have confirmed the safety and efficacy of SVV as a cancer treatment. We determine the atomic structures for SVV–ANTXR1 in different conditions. A most attractive finding is that a serine-to-alanine mutation at VP2 177 position on the interface significantly increases proliferation. The molecular details for SVV–ANTXR1 attachment and uncoating shown in this work provide clues to optimize SVV as an oncolytic reagent with higher efficacy and lower immunogenicity.