{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:55:20Z","timestamp":1790355320764,"version":"4.1.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"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":[[2015,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Enterovirus (EV) is one of the major causative agents of hand, foot, and mouth disease in the Pacific-Asia region. In particular, EV71 causes severe central nervous system infections, and the fatality rates from EV71 infection are high. Moreover, an outbreak of respiratory illnesses caused by an emerging EV, EV68, recently occurred among over 1,000 young children in the United States and was also associated with neurological infections. Although enterovirus has emerged as a considerable global public health threat, no antiviral drug for clinical use is available. In the present work, we screened our compound library for agents targeting viral protease and identified a peptidyl aldehyde, NK-1.8k, that inhibits the proliferation of different EV71 strains and one EV68 strain and that had a 50% effective concentration of 90 nM. Low cytotoxicity (50% cytotoxic concentration, &gt;200 \u03bcM) indicated a high selective index of over 2,000. We further characterized a single amino acid substitution inside protease 3C (3C\n            <jats:sup>pro<\/jats:sup>\n            ), N69S, which conferred EV71 resistance to NK-1.8k, possibly by increasing the flexibility of the substrate binding pocket of 3C\n            <jats:sup>pro<\/jats:sup>\n            . The combination of NK-1.8k and an EV71 RNA-dependent RNA polymerase inhibitor or entry inhibitor exhibited a strong synergistic anti-EV71 effect. Our findings suggest that NK-1.8k could potentially be developed for anti-EV therapy.\n          <\/jats:p>","DOI":"10.1128\/aac.00049-15","type":"journal-article","created":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T03:01:46Z","timestamp":1424228506000},"page":"2636-2646","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Peptidyl Aldehyde NK-1.8k Suppresses Enterovirus 71 and Enterovirus 68 Infection by Targeting Protease 3C"],"prefix":"10.1128","volume":"59","author":[{"given":"Yaxin","family":"Wang","sequence":"first","affiliation":[{"name":"National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, China"},{"name":"University of Chinese Academy of Science, Chinese Academy of Science, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Yang","sequence":"additional","affiliation":[{"name":"Phillips Academy, Andover, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Zhai","sequence":"additional","affiliation":[{"name":"College of Pharmacy &amp; State Key Laboratory of Elemento-Organic Chemistry, Nankai University, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Pharmacy &amp; State Key Laboratory of Elemento-Organic Chemistry, Nankai University, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), 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"}]},{"given":"Zihe","family":"Rao","sequence":"additional","affiliation":[{"name":"National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, China"},{"name":"College of Pharmacy &amp; State Key Laboratory of Elemento-Organic Chemistry, Nankai University, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, China"},{"name":"University of Chinese Academy of Science, Chinese Academy of Science, Beijing, China"},{"name":"Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2013.12.008"},{"key":"e_1_3_2_3_2","first-page":"200","article-title":"Acute flaccid paralysis in infants and young children with enterovirus 71 infection: MR imaging findings and clinical correlates","volume":"22","author":"Chen CY","year":"2001","unstructured":"Chen CY, Chang YC, Huang CC, Lui CC, Lee KW, Huang SC. 2001. 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