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Lymphocytic choriomeningitis virus (LCMV) is a worldwide-distributed, prototypic OW mammarenavirus of clinical significance that has been largely neglected as a human pathogen. No licensed OW mammarenavirus vaccines are available, and the current therapeutic option is limited to the off-label use of ribavirin, which offers only partial efficacy. This situation underscores the urgent need to develop novel antivirals against human pathogenic mammarenaviruses. Previously, we showed that afatinib, a pan-ErbB tyrosine kinase inhibitor, inhibited multiple steps of the life cycles of OW LASV and LCMV, as well as the New World Jun\u00edn virus vaccine strain Candid#1. In the present study, we investigated the inhibitory effect of U-73122, a phospholipase C inhibitor that acts downstream of ErbB signalling, on LCMV multiplication. U-73122 inhibited WT recombinant (r) LCMV multiplication in cultured cells. Preincubation of cell-free LCMV virions with U-73122 resulted in impaired virion infectivity. U-73122 also inhibited the infection of rLCMVs expressing heterologous viral glycoproteins, including the vesicular stomatitis Indiana virus (VSIV) glycoprotein, whereas WT VSIV infection was not affected by U-73122 treatment. Our results show the novel bioactivity of U-73122 as an LCMV inhibitor and indicate the presence of a virion-associated molecule that is necessary for virion infectivity and can be exploited as a potential antiviral drug target against human pathogenic mammarenavirus infections.<\/jats:p>","DOI":"10.1099\/jgv.0.002060","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T16:16:30Z","timestamp":1734452190000},"source":"Crossref","is-referenced-by-count":0,"title":["U-73122, a phospholipase C inhibitor, impairs lymphocytic choriomeningitis virus virion infectivity"],"prefix":"10.1099","volume":"105","author":[{"given":"Keita","family":"Mizuma","sequence":"first","affiliation":[{"name":"Present address: Division of Risk Analysis and Management, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, Japan"},{"name":"Laboratory of Emerging Viral Diseases, International Research Center for Infectious Diseases, Research 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