{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T12:19:37Z","timestamp":1773058777732,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A helicase\u2010primase inhibitor, amenamevir (ASP2151), is the active pharmaceutical ingredient of a drug for the herpes zoster that is caused by reactivation of varicella\u2010zoster virus (VZV). Here we report a new amenamevir\u2010resistant VZV isolated under the selection pressure of amenamevir. The resistant virus has a nonsynonymous mutation K350N in the helicase gene ORF55. A recombinant virus artificially constructed harboring the ORF55 K350N also acquired amenamevir resistance, and thus the single amino\u2010acid substitution in helicase is revealed to be responsible for the resistance. We observed that the drug\u2010resistant virus and the ORF55 K350N recombinant virus have high resistance to amenamevir, as the EC\n                    <jats:sub>50<\/jats:sub>\n                    values in a plaque reduction assay were &gt;\u2009100\u2009\u03bcM, while the two viruses remained susceptible to the nucleoside analog drug acyclovir. No defect in viral growth was observed for these resistant viruses in a plaque size assay in human malignant melanoma cells. However, defect in plaque formation was observed from resistant virus in human fetal lung fibroblast cells, showing that the growth of the resistant virus is dependent on the cell type. We observed that the single amino\u2010acid substitution in the helicase induces amenamevir resistance, confirming the importance of the helicase in amenamevir's inhibition of virus growth. Our findings highlight the importance of regulating the clinical use of amenamevir to minimize the risk of the emergence of helicase K350N mutation, especially in the long\u2010term use of amenamevir by immunosuppressed patients.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70080","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T04:31:48Z","timestamp":1732163508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Single Amino Acid Substitution Within the Helicase of Varicella Zoster Virus Makes It Resistant to Amenamevir"],"prefix":"10.1002","volume":"96","author":[{"given":"Gema Barlian","family":"Effendi","sequence":"first","affiliation":[{"name":"Division of Clinical Virology, Center for Infectious Diseases Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaito","family":"Aoki","sequence":"additional","affiliation":[{"name":"Division of Clinical Virology, Center for Infectious Diseases Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Istiqomah","family":"Marini","sequence":"additional","affiliation":[{"name":"Division of Clinical Virology, Center for Infectious Diseases Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rei","family":"Takamiya","sequence":"additional","affiliation":[{"name":"Division of Clinical Virology, Center for Infectious Diseases Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanako","family":"Ishimaru","sequence":"additional","affiliation":[{"name":"Division of Clinical Virology, Center for Infectious Diseases Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuhiro","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Division of Clinical Virology, Center for Infectious Diseases Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6595-8522","authenticated-orcid":false,"given":"Yasuko","family":"Mori","sequence":"additional","affiliation":[{"name":"Division of Clinical Virology, Center for Infectious Diseases Kobe University Graduate School of Medicine Kobe 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