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Outbreaks occur regularly, especially in the Asia-Pacific region, putting a burden on public healthcare systems. Currently, there is no antiviral for treating this infectious disease and the only vaccines are limited to circulation in China, presenting an unmet medical need that needs to be filled urgently. The human enterovirus 3\u2009C protease has been deemed a plausible drug target due to its essential roles in viral replication. In this study, we designed and synthesized 10 analogues of the Rhinovirus 3\u2009C protease inhibitor, Rupintrivir and tested their 3\u2009C protease inhibitory activities followed by a cellular assay using human enterovirus 71 (EV71)-infected human RD cells. Our results revealed that a peptide-based compound containing a trifluoromethyl moiety to be the most potent analogue, with an EC<jats:sub>50<\/jats:sub> of 65\u2009nM, suggesting its potential as a lead for antiviral drug discovery.<\/jats:p>","DOI":"10.1038\/srep33663","type":"journal-article","created":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T10:45:31Z","timestamp":1474368331000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Antiviral activities of peptide-based covalent inhibitors of the Enterovirus 71 3C protease"],"prefix":"10.1038","volume":"6","author":[{"given":"Yong Wah","family":"Tan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melgious Jin Yan","family":"Ang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiu Ying","family":"Lau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Poulsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fui Mee","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siew Wen","family":"Then","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhe","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Hill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan Jin","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng San Brian","family":"Chia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin Jang Hann","family":"Chu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,9,20]]},"reference":[{"key":"BFsrep33663_CR1","doi-asserted-by":"publisher","first-page":"915","DOI":"10.7754\/Clin.Lab.2012.121123","volume":"59","author":"A Roohandeh","year":"2013","unstructured":"Roohandeh, A. et al. 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