{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T09:31:38Z","timestamp":1773048698010,"version":"3.50.1"},"reference-count":194,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T00:00:00Z","timestamp":1683763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disease and Stroke","doi-asserted-by":"publisher","award":["R35NS5271118"],"award-info":[{"award-number":["R35NS5271118"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Brown University","award":["R35NS5271118"],"award-info":[{"award-number":["R35NS5271118"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease caused by infection with JC Polyomavirus (JCPyV). Despite the identification of the disease and isolation of the causative pathogen over fifty years ago, no antiviral treatments or prophylactic vaccines exist. Disease onset is usually associated with immunosuppression, and current treatment guidelines are limited to restoring immune function. This review summarizes the drugs and small molecules that have been shown to inhibit JCPyV infection and spread. Paying attention to historical developments in the field, we discuss key steps of the virus lifecycle and antivirals known to inhibit each event. We review current obstacles in PML drug discovery, including the difficulties associated with compound penetrance into the central nervous system. We also summarize recent findings in our laboratory regarding the potent anti-JCPyV activity of a novel compound that antagonizes the virus-induced signaling events necessary to establish a productive infection. Understanding the current panel of antiviral compounds will help center the field for future drug discovery efforts.<\/jats:p>","DOI":"10.3390\/ijms24108580","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T04:29:01Z","timestamp":1683779341000},"page":"8580","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["An Elusive Target: Inhibitors of JC Polyomavirus Infection and Their Development as Therapeutics for the Treatment of Progressive Multifocal Leukoencephalopathy"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8192-5676","authenticated-orcid":false,"given":"Jacob","family":"Kaiserman","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bethany A.","family":"O\u2019Hara","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheila A.","family":"Haley","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3763-9073","authenticated-orcid":false,"given":"Walter J.","family":"Atwood","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Polyomaviridae Study Group of the International Committee on Taxonomy of Viruses, Calvignac-Spencer, S., Feltkamp, M.C., Daugherty, M.D., Moens, U., Ramqvist, T., Johne, R., and Ehlers, B. 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