{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:12:35Z","timestamp":1783444355833,"version":"3.54.6"},"reference-count":29,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2015,6,17]],"date-time":"2015-06-17T00:00:00Z","timestamp":1434499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Enterovirus A71 (EV-A71) in the Picornaviridae family causes hand-foot-and-mouth disease, aseptic meningitis, severe central nervous system disease, even death. EV-A71 2A protease cleaves Type I interferon (IFN)-\u03b1\/\u03b2 receptor 1 (IFNAR1) to block IFN-induced Jak\/STAT signaling. This study investigated anti-EV-A7l activity and synergistic mechanism(s) of a novel furoquinoline alkaloid compound CW-33 alone and in combination with IFN-\u03b2 Anti-EV-A71 activities of CW-33 alone and in combination with IFN-\u03b2 were evaluated by inhibitory assays of virus-induced apoptosis, plaque formation, and virus yield. CW-33 showed antiviral activities with an IC50 of near 200 \u00b5M in EV-A71 plaque reduction and virus yield inhibition assays. While, anti-EV-A71 activities of CW-33 combined with 100 U\/mL IFN-\u03b2 exhibited a synergistic potency with an IC50 of approximate 1 \u00b5M in plaque reduction and virus yield inhibition assays. Molecular docking revealed CW-33 binding to EV-A71 2A protease active sites, correlating with an inhibitory effect of CW33 on in vitro enzymatic activity of recombinant 2A protease IC50 = 53.1 \u00b5M). Western blotting demonstrated CW-33 specifically inhibiting 2A protease-mediated cleavage of IFNAR1. CW-33 also recovered Type I IFN-induced Tyk2 and STAT1 phosphorylation as well as 2',5'-OAS upregulation in EV-A71 infected cells. The results demonstrated CW-33 inhibiting viral 2A protease activity to reduce Type I IFN antagonism of EV-A71. Therefore, CW-33 combined with a low-dose of Type I IFN could be applied in developing alternative approaches to treat EV-A71 infection.<\/jats:p>","DOI":"10.3390\/v7062764","type":"journal-article","created":{"date-parts":[[2015,6,17]],"date-time":"2015-06-17T11:19:34Z","timestamp":1434539974000},"page":"3155-3171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Antiviral Potential of a Novel Compound CW-33 against Enterovirus A71 via Inhibition of Viral 2A Protease"],"prefix":"10.3390","volume":"7","author":[{"given":"Ching-Ying","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan"},{"name":"School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An-Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nursing, St. Mary's Junior College of Medicine, Nursing and Management, Yilan County 266, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mann-Jen","family":"Hour","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Asia University, Wufeng, Taichung 41354, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szu-Hao","family":"Kung","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Hsien","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Chieh","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Shiun","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1211-0245","authenticated-orcid":false,"given":"Jin-Cherng","family":"Lien","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Biotechnology, Asia University, Wufeng, Taichung 41354, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.3201\/eid0903.020285","article-title":"Enterovirus 71 outbreaks, Taiwan: Occurrence and recognition","volume":"9","author":"Lin","year":"2003","journal-title":"Emerg. 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