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The Z protein and SSP undergo N-terminal myristoylation by host cell N-myristoyltransferases (NMT1 and NMT2), and G2A mutations that prevent myristoylation of Z or SSP have been shown to affect Z mediated virus budding and GP2 mediated fusion activity required to complete the virus cell entry process. In the present work, we present evidence that the validated on-target specific pan NMT inhibitor DDD85464 exerts a potent antiviral activity against the prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV) that correlated with reduced Z budding activity and GP2 mediated fusion activity, as well as proteasome mediated degradation of the Z protein. The potent anti-mammarenaviral activity of DDD85646 was also observed with the hemorrhagic fever causing mammarenaviruses Junin (JUNV) and Lassa (LASV) viruses. Our results support exploration of NMT inhibition as a broad-spectrum antiviral against human pathogenic mammarenaviruses.<\/jats:p>","DOI":"10.1101\/2024.08.01.606235","type":"posted-content","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T00:55:11Z","timestamp":1722560111000},"source":"Crossref","is-referenced-by-count":5,"title":["Cellular N-myristoyl transferases Are Required for Mammarenavirus Multiplication"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0174-8454","authenticated-orcid":false,"given":"Haydar","family":"Witwit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Betancourt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8048-410X","authenticated-orcid":false,"given":"Beatrice","family":"Cubitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9142-4483","authenticated-orcid":false,"given":"Roaa","family":"Khafaji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0293-9612","authenticated-orcid":false,"given":"Heinrich","family":"Kowalski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1934-9494","authenticated-orcid":false,"given":"Chengjin","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7084-0804","authenticated-orcid":false,"given":"Luis","family":"Martinez-Sobrido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"de la Torre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024080423551171000_2024.08.01.606235v1.1","unstructured":"Radoshitzky, S.R. , Buchmeier, M.J. , de la Torre, J.C. 2022 Fields Virology: Emerging Viruses: Arenaviridae. 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