{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:56:41Z","timestamp":1792702601994,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Dengue virus (DENV) is an acute infectious pathogen worldwide, for which no effective therapeutics are available. The RNA\u2010dependent RNA polymerase (RdRp) displays an important role during DENV replication and is therefore a promising target in the development of antiviral drugs. However, there are still no clinically approved RdRp inhibitors available. In this study, we identified a natural small molecule, 12\u03b2\u2010hydroxydammar\u20103\u2010one\u201020(S)\u2010O\u2010\u03b2\u2010\n                    <jats:sc>d<\/jats:sc>\n                    \u2010glucopyranoside (PN\u20101), using a surface plasmon resonance\u2010based screening assay. Biochemical and structural analyses revealed that PN\u20101 selectively targets the RdRp of DENV NS5 protein by covalently modifying residues Glu255, Met387, Glu479, and Ala507. Mechanistic studies involving tryptophan scanning and hydrogen\u2010deuterium exchange mass spectrometry revealed that PN\u20101 binding regulates RdRp conformational transitions. This allosteric mechanism leads to suppression of enzymatic activity and inhibition of DENV replication. Consequently, PN\u20101 exhibited potent antiviral activity across various cell lines and conferred significant protection in both ICR suckling and AG129 mouse models. Taken together, our results show that PN\u20101 functions as a novel non\u2010nucleoside inhibitor to suppress DENV replication by targeting RdRp. These findings highlight PN\u20101 as a promising anti\u2010DENV lead compound, while revealing conserved RdRp residues as actionable targets for rational drug design.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70514","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T07:04:02Z","timestamp":1764486242000},"source":"Crossref","is-referenced-by-count":4,"title":["Discovery of a Novel Non\u2010Nucleoside Inhibitor of RNA\u2010Dependent RNA Polymerase Against Dengue Virus"],"prefix":"10.1002","volume":"6","author":[{"given":"Xue\u2010Mei","family":"He","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Southern Medical University  Guangzhou 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