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The repurposing of pharmaceutical drugs for use as antivirals is emerging as a cost\u2010 and time\u2010 efficient approach to developing HTAs for the treatment of a variety of viral infections. In this study, we used a virus titer method to screen 30 small molecules for antiviral activity against Herpes simplex virus\u20101 (HSV\u20101). We found that the small molecule RAF265, an anticancer drug that has been shown to be a potent inhibitor of B\u2010RAF V600E, reduced viral loads of HSV\u20101 by 4 orders of magnitude in Vero cells and reduced virus proliferation in vivo. RAF265\u00a0mediated cytoskeleton rearrangement and targeted the host cell's translation machinery, which suggests that the antiviral activity of RAF265 may be attributed to a dual inhibition strategy. This study offers a starting point for further advances toward clinical development of antivirals against HSV\u20101.<\/jats:p>","DOI":"10.1002\/jmv.28226","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T13:46:21Z","timestamp":1666014381000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Small molecule RAF265 as an antiviral therapy acts against HSV\u20101 by regulating cytoskeleton rearrangement and cellular translation machinery"],"prefix":"10.1002","volume":"95","author":[{"given":"Cui\u2010Cui","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, Department of Veterinary Medicine China Agricultural University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Jing","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology 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