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There are limited treatment options for patients diagnosed with PML, and most involve reconstitution of immunological functions. In this paper, we show that flavonols, specifically quercetin, myricetin, and fisetin, significantly reduce JCPyV infection in human glial cells. We further show that quercetin and fisetin can suppress viral spread in an already established infection, suggesting therapeutic viability of these drugs as antivirals. Additional research is required to determine the mechanism of action of flavonols in inhibiting JCPyV infection and to investigate whether these compounds have the potential to cross the blood-brain barrier in significant amounts to inhibit the virus in the brain parenchyma.<\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>The human polyomavirus, JC polyomavirus (JCPyV), causes significant morbidity and mortality in immunosuppressed or immunomodulated patients. There are no approved antivirals to treat JCPyV-induced disease. Flavonols are naturally occurring polyphenolic compounds that are known to antagonize pathways involved in JCPyV infection. Several flavonols were found to inhibit initial JCPyV infection and viral spread in a glial cell line and in normal human glial cells. These represent a promising new treatment paradigm for patients at risk of suffering from JCPyV-induced disease.<\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.01527-25","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T13:00:27Z","timestamp":1755781227000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Therapeutic potential of flavonols in the treatment of JCPyV"],"prefix":"10.1128","volume":"13","author":[{"given":"Evan","family":"MacLure","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Biochemistry, and Molecular Biology, Brown University","place":["Providence, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5385-4889","authenticated-orcid":true,"given":"Kaitlin","family":"Garabian","sequence":"additional","affiliation":[{"name":"Department of Cell 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