{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:13:51Z","timestamp":1790648031959,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010662","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000}}],"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"CDC Intramural Research"},{"DOI":"10.13039\/100012399","name":"Biomedical Advanced Research and Development Authority","doi-asserted-by":"publisher","award":["HHS-ASPR-22-0091"],"award-info":[{"award-number":["HHS-ASPR-22-0091"]}],"id":[{"id":"10.13039\/100012399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C29637\/A20183"],"award-info":[{"award-number":["C29637\/A20183"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C29637\/A21451"],"award-info":[{"award-number":["C29637\/A21451"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["752165"],"award-info":[{"award-number":["752165"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["PS1042"],"award-info":[{"award-number":["PS1042"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["PS1042"],"award-info":[{"award-number":["PS1042"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    We have recently shown that the replication of rhinovirus, poliovirus and foot-and-mouth disease virus requires the co-translational\n                    <jats:italic>N-<\/jats:italic>\n                    myristoylation of viral proteins by human host cell\n                    <jats:italic>N<\/jats:italic>\n                    -myristoyltransferases (NMTs), and is inhibited by treatment with IMP-1088, an ultrapotent small molecule NMT inhibitor. Here, we examine the importance of\n                    <jats:italic>N<\/jats:italic>\n                    -myristoylation during vaccinia virus (VACV) infection in primate cells and demonstrate the anti-poxviral effects of IMP-1088.\n                    <jats:italic>N-<\/jats:italic>\n                    myristoylated proteins from VACV and the host were metabolically labelled with myristic acid alkyne during infection using quantitative chemical proteomics. We identified VACV proteins A16, G9 and L1 to be\n                    <jats:italic>N-<\/jats:italic>\n                    myristoylated. Treatment with NMT inhibitor IMP-1088 potently abrogated VACV infection, while VACV gene expression, DNA replication, morphogenesis and EV formation remained unaffected. Importantly, we observed that loss of\n                    <jats:italic>N<\/jats:italic>\n                    -myristoylation resulted in greatly reduced infectivity of assembled mature virus particles, characterized by significantly reduced host cell entry and a decline in membrane fusion activity of progeny virus. While the\n                    <jats:italic>N<\/jats:italic>\n                    -myristoylation of VACV entry proteins L1, A16 and G9 was inhibited by IMP-1088, mutational and genetic studies demonstrated that the\n                    <jats:italic>N<\/jats:italic>\n                    -myristoylation of L1 was the most critical for VACV entry. Given the significant genetic identity between VACV, monkeypox virus and variola virus L1 homologs, our data provides a basis for further investigating the role of\n                    <jats:italic>N<\/jats:italic>\n                    -myristoylation in poxviral infections as well as the potential of selective NMT inhibitors like IMP-1088 as broad-spectrum poxvirus inhibitors.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010662","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T13:57:03Z","timestamp":1665410223000},"page":"e1010662","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":38,"title":["Inhibition of vaccinia virus L1 N-myristoylation by the host N-myristoyltransferase inhibitor IMP-1088 generates non-infectious virions defective in cell entry"],"prefix":"10.1371","volume":"18","author":[{"given":"Lalita","family":"Priyamvada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter W.","family":"Kallemeijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Faronato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Wilkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia S.","family":"Goldsmith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Cotter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suany","family":"Ojeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Solari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Moss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward W.","family":"Tate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1472-1418","authenticated-orcid":true,"given":"Panayampalli Subbian","family":"Satheshkumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,10,10]]},"reference":[{"issue":"1","key":"ppat.1010662.ref001","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1600-065X.2010.00975.x","article-title":"Smallpox vaccines: targets of protective immunity","volume":"239","author":"B. 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