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EV\u2010A71, EV\u2010D68, poliovirus (PV), and coxsackievirus (CV) outbreaks have affected millions worldwide, causing a range of upper respiratory, skin, and neuromuscular diseases, including acute flaccid myelitis, and hand\u2010foot\u2010and\u2010mouth disease. There are no FDA\u2010approved antiviral therapeutics for these enteroviruses. This study describes novel antiviral compounds targeting the conserved non\u2010structural viral protein 2C with low micromolar to nanomolar IC\n                    <jats:sub>50<\/jats:sub>\n                    values. The selection of resistant mutants resulted in amino acid substitutions in the viral capsid protein, implying these compounds may play a role in inhibiting the interaction of 2C and the capsid protein. The assembly and encapsidation stages of the viral life cycle still need to be fully understood, and the inhibitors reported here could be useful probes in understanding these processes.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202200541","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T22:10:48Z","timestamp":1676499048000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Development of Enterovirus Antiviral Agents That Target the Viral 2C Protein"],"prefix":"10.1002","volume":"18","author":[{"given":"Rishabh","family":"Kejriwal","sequence":"first","affiliation":[{"name":"Biology\/Physics Building Department of Molecular and Cell Biology University of Connecticut  91 North Eagleville Road, Unit-3125 Storrs CT 06269-3125 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan","family":"Evans","sequence":"additional","affiliation":[{"name":"Biology\/Physics Building Department of Molecular and Cell Biology University of Connecticut  91 North Eagleville Road, Unit-3125 Storrs CT 06269-3125 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Biology\/Physics Building Department of Molecular and Cell Biology University of Connecticut  91 North Eagleville Road, Unit-3125 Storrs CT 06269-3125 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Swistak","sequence":"additional","affiliation":[{"name":"Institut Pasteur Universit\u00e9 Paris Cit\u00e9 Dynamics of Host-Pathogen Interactions Unit  75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Alexandrescu","sequence":"additional","affiliation":[{"name":"Biology\/Physics Building Department of Molecular and Cell Biology University of Connecticut  91 North Eagleville Road, Unit-3125 Storrs CT 06269-3125 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Cohen","sequence":"additional","affiliation":[{"name":"Biology\/Physics Building Department of Molecular and Cell Biology University of Connecticut  91 North Eagleville Road, Unit-3125 Storrs CT 06269-3125 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahian","family":"Rahman","sequence":"additional","affiliation":[{"name":"Biology\/Physics Building Department of Molecular and Cell Biology University of Connecticut  91 North Eagleville Road, Unit-3125 Storrs CT 06269-3125 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niel","family":"Henriksen","sequence":"additional","affiliation":[{"name":"Atomwise Inc.  717 Market St #800 San Francisco CA 94103 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radha","family":"Charan Dash","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Connecticut  69 North Eagleville Road, Unit 3092 Storrs CT 06029-3092 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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