{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:54:49Z","timestamp":1784872489628,"version":"3.55.0"},"reference-count":58,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Enterovirus 71 (EV71) (\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Picornaviridae<\/jats:named-content>\n            family) and hepatitis C virus (HCV) (\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Flaviviridae<\/jats:named-content>\n            family) are the causative agents of human hand, foot, and mouth disease (HFMD) and hepatitis C, resulting in a severe pandemic involving millions of infections in the Asia-Pacific region and worldwide. The great impact of EV71 and HCV on public health highlights the need to further our understanding of the biology of these two viruses and develop effective therapeutic antivirals. Here, we evaluated a total of 32 lycorine derivatives and demonstrated that 1-acetyllycorine suppressed the proliferation of multiple strains of EV71 in various cells. The results of the drug resistance analysis revealed that 1-acetyllycorine targeted a phenylalanine (F76) in EV71 2A protease (2A\n            <jats:sup>pro<\/jats:sup>\n            ) to stabilize the conformation of a unique zinc finger. Most interestingly, the zinc binding site in EV71 2A\n            <jats:sup>pro<\/jats:sup>\n            is the exclusive homolog of HCV NS3 among all viruses. Further analysis revealed that 1-acetyllycorine also inhibits HCV with high efficacy, and the mutation on R118 in HCV NS3, which corresponds to F76 in EV71 2A\n            <jats:sup>pro<\/jats:sup>\n            , confers the resistance of HCV to 1-acetyllycorine. These results revealed a conserved mechanism of 1-acetyllycorine against EV71 and HCV through targeting viral proteases. We also documented the significant synergistic anti-EV71 and anti-HCV effects of 1-acetyllycorine with reported inhibitors, supporting potential combination therapy for the treatment of EV71 and HCV infections.\n          <\/jats:p>","DOI":"10.1128\/aac.02274-15","type":"journal-article","created":{"date-parts":[[2015,11,24]],"date-time":"2015-11-24T02:43:29Z","timestamp":1448333009000},"page":"913-924","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["A Conserved Inhibitory Mechanism of a Lycorine Derivative against Enterovirus and Hepatitis C Virus"],"prefix":"10.1128","volume":"60","author":[{"given":"Yu","family":"Guo","sequence":"first","affiliation":[{"name":"College of Pharmacy and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China"},{"name":"Collaborative Innovation Center for Biotherapy, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Pharmacy and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China"},{"name":"Collaborative Innovation Center for Biotherapy, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Qing","sequence":"additional","affiliation":[{"name":"Tsinghua-Peking Center for Life Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, China"},{"name":"School of Medicine, Tsinghua University, Beijing, China"},{"name":"Collaborative Innovation Center for Biotherapy, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qizhen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luqing","family":"Shang","sequence":"additional","affiliation":[{"name":"College of Pharmacy and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Pharmacy and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuna","family":"Sun","sequence":"additional","affiliation":[{"name":"National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2009.01.015"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-7-94"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000332374"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2008.01934.x"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02733-12"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01712-12"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2013.07.006"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2002.tb00601.x"},{"key":"e_1_3_1_10_2","first-page":"685","volume-title":"Fields virology","author":"Racaniello VR","year":"2001","unstructured":"Racaniello VR. 2001. 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