{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:03:17Z","timestamp":1784761397615,"version":"3.55.0"},"reference-count":124,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":41,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Alberta Ministry of Technology and Innovation"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19AI171292"],"award-info":[{"award-number":["U19AI171292"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The therapeutic value of antiviral nucleoside analogs was highlighted during the coronavirus disease 2019 (COVID-19) pandemic, with remdesivir and molnupiravir repurposed for their broad-spectrum antiviral activity. The cytidine analog azvudine (FNC) has recently gained attention as a potential treatment for human immunodeficiency virus type 1 (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Considering the distinct substrate specificities of HIV-1 reverse transcriptase (RT) and SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), a unifying mechanism of inhibition remains elusive. Here, we assessed the inhibitory effects of FNC\u2019s active triphosphate form, FNC-TP, across several viral polymerases. The relative efficiency of FNC-TP incorporation followed the order: HIV-1 RT\u00a0&amp;gt;\u00a0hepatitis C virus (HCV) RdRp\u00a0&amp;gt;\u00a0respiratory syncytial virus (RSV) RdRp\u00a0&amp;gt;\u00a0dengue virus type 2 (DENV-2) RdRp \u226b SARS-CoV-2 RdRp. Its incorporation caused chain-termination in all polymerases tested. Antiviral activity against HIV-1 has previously been demonstrated and is here shown with DENV-2. Collectively, the data show that inhibition of viral polymerases by FNC-TP can translate to antiviral activity against both retroviruses and RNA viruses, but the link is not evident for SARS-CoV-2. FNC-TP is a poor substrate for SARS-CoV-2 RdRp, and FNC lacks significant antiviral activity against SARS-CoV-2 in cell culture.<\/jats:p>","DOI":"10.1093\/narmme\/ugaf029","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T23:25:39Z","timestamp":1755041139000},"source":"Crossref","is-referenced-by-count":8,"title":["Mechanism and spectrum of inhibition of viral polymerases by 2\u2032-deoxy-2\u2032-\u03b2-fluoro-4\u2032-azidocytidine or azvudine"],"prefix":"10.1093","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3981-0284","authenticated-orcid":false,"given":"Hery\u00a0W","family":"Lee","sequence":"first","affiliation":[{"name":"University of Alberta Department of Medical Microbiology & Immunology, , Edmonton , AB T6G 2E1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egor\u00a0P","family":"Tchesnokov","sequence":"additional","affiliation":[{"name":"University of Alberta Department of Medical Microbiology & Immunology, , Edmonton , AB T6G 2E1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura\u00a0J","family":"Stevens","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center Department of Pediatrics, , Nashville , TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tia\u00a0M","family":"Hughes","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center Department of Pediatrics, , Nashville , TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan\u00a0V","family":"Diefenbacher","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill Department of Epidemiology, , Chapel Hill, NC 27599 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Woolner","sequence":"additional","affiliation":[{"name":"University of Alberta Department of Medical Microbiology & Immunology, , Edmonton , AB T6G 2E1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Kocincova","sequence":"additional","affiliation":[{"name":"University of Alberta Department of Medical Microbiology & Immunology, , Edmonton , AB T6G 2E1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7890-8815","authenticated-orcid":false,"given":"David\u00a0C","family":"Schultz","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Department of Biochemistry and Biophysics, , Philadelphia , PA 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3956-6610","authenticated-orcid":false,"given":"Sara","family":"Cherry","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Department of Biochemistry and Biophysics, , Philadelphia , PA 19104 ,","place":["United States"]},{"name":"Perelman School of Medicine, University of Pennsylvania Department of Pathology and Laboratory Medicine, , Philadelphia , PA 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9181-2183","authenticated-orcid":false,"given":"Timothy\u00a0P","family":"Sheahan","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill Department of Epidemiology, , Chapel Hill, NC 27599 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2655-0900","authenticated-orcid":false,"given":"Mark\u00a0R","family":"Denison","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center Department of Pediatrics, , Nashville , TN 37232 ,","place":["United States"]},{"name":"Vanderbilt Institute for Infection, Immunology, and Inflammation , Nashville , TN 37232 ,","place":["United States"]},{"name":"Microbiology, and Immunology, Vanderbilt University Medical Center Department of Pathology, , Nashville , TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6213-5806","authenticated-orcid":false,"given":"Matthias","family":"G\u00f6tte","sequence":"additional","affiliation":[{"name":"University of Alberta Department of Medical Microbiology & Immunology, , Edmonton , AB T6G 2E1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"2025090111020801900_B1","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1056\/NEJMoa2007764","article-title":"Remdesivir for the treatment of COVID-19\u2014final report","volume":"383","author":"Beigel","year":"2020","journal-title":"N Engl J Med"},{"key":"2025090111020801900_B2","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1021\/acscentsci.0c00489","article-title":"Remdesivir: a review of its discovery and development leading to emergency use authorization for treatment of COVID-19","volume":"6","author":"Eastman","year":"2020","journal-title":"ACS Cent Sci"},{"key":"2025090111020801900_B3","doi-asserted-by":"publisher","first-page":"6233","DOI":"10.3390\/v7122934","article-title":"Identification of a new ribonucleoside inhibitor of Ebola virus 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