{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:49:39Z","timestamp":1786978179895,"version":"build-2736575974"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The ongoing evolution of SARS\u2010CoV\u20102 and its immune\u2010evading variants underscores an urgent requirement for broad\u2010spectrum antiviral drugs. In this study, a series of lycorine derivatives was synthesized. This led to the identification of compound\n                    <jats:bold>7<\/jats:bold>\n                    as a promising antiviral candidate. Compound\n                    <jats:bold>7<\/jats:bold>\n                    exhibited potent inhibitory activity against SARS\u2010CoV\u20102 and its variants, including Alpha, Beta, Delta, and Omicron, in vitro. The antiviral efficacy of compound\n                    <jats:bold>7<\/jats:bold>\n                    was then validated in vivo. Treatment with compound\n                    <jats:bold>7<\/jats:bold>\n                    significantly reduced viral loads and alleviated lung pathologies in SARS\u2010CoV\u20102\u2010infected hamsters. Mechanistically, compound\n                    <jats:bold>7<\/jats:bold>\n                    directly targeted the short isoform of the zinc\u2010finger antiviral protein (ZAP\u2010S) and bound to specific residues (E111, E115, and F549). This result was confirmed using cellular thermal shift assays, bio\u2010layer interferometry, and mutagenesis studies. This interaction enhanced the ZAP\u2010S stability and disrupted \u20131 programmed ribosomal frameshifting (\u20131PRF), a critical process for viral polyprotein synthesis. The antiviral activity of compound\n                    <jats:bold>7<\/jats:bold>\n                    was ZAP\u2010S\u2010dependent, as ZAP\u2010S knockdown abolished its efficacy while overexpression enhanced it. These results established compound\n                    <jats:bold>7<\/jats:bold>\n                    as a novel antiviral candidate that can combat SARS\u2010CoV\u20102 and its variants by targeting ZAP to inhibit \u20131PRF. This compound, therefore, represents a promising therapeutic strategy.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70715","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:08:20Z","timestamp":1775538500000},"source":"Crossref","is-referenced-by-count":1,"title":["Lycorine Derivative Inhibits SARS\u2010CoV\u20102 Replication by Reducing \u22121 Programmed Ribosomal Frameshifting via Targeting ZAP"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9814-0081","authenticated-orcid":false,"given":"Tingfu","family":"Du","sequence":"first","affiliation":[{"name":"Institute of Medical Biology Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixue","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Health and Multimorbidity National Center of Technology Innovation 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Peking Union Medical College  Beijing China"},{"name":"Department of Molecular Biology and Biochemistry Institute of Basic Medical Sciences Medical Primate Research Center Neuroscience Center Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing 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