{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T18:03:48Z","timestamp":1774116228014,"version":"3.50.1"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"20","license":[{"start":{"date-parts":[[2011,10,15]],"date-time":"2011-10-15T00:00:00Z","timestamp":1318636800000},"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":["J Virol"],"published-print":{"date-parts":[[2011,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Members of the\n            <jats:named-content content-type=\"genus-species\">Enterovirus<\/jats:named-content>\n            genus of the\n            <jats:named-content content-type=\"genus-species\">Picornaviridae<\/jats:named-content>\n            family are abundant, with common human pathogens that belong to the rhinovirus (HRV) and enterovirus (EV) species, including diverse echo-, coxsackie- and polioviruses. They cause a wide spectrum of clinical manifestations ranging from asymptomatic to severe diseases with neurological and\/or cardiac manifestations. Pandemic outbreaks of EVs may be accompanied by meningitis and\/or paralysis and can be fatal. However, no effective prophylaxis or antiviral treatment against most EVs is available. The EV RNA genome directs the synthesis of a single polyprotein that is autocatalytically processed into mature proteins at Gln\u2193Gly cleavage sites by the 3C protease (3C\n            <jats:sup>pro<\/jats:sup>\n            ), which has narrow, conserved substrate specificity. These cleavages are essential for virus replication, making 3C\n            <jats:sup>pro<\/jats:sup>\n            an excellent target for antivirus drug development. In this study, we report the first determination of the crystal structure of 3C\n            <jats:sup>pro<\/jats:sup>\n            from an enterovirus B, EV-93, a recently identified pathogen, alone and in complex with the anti-HRV molecules compound 1 (AG7404) and rupintrivir (AG7088) at resolutions of 1.9, 1.3, and 1.5 \u00c5, respectively. The EV-93 3C\n            <jats:sup>pro<\/jats:sup>\n            adopts a chymotrypsin-like fold with a canonically configured oxyanion hole and a substrate binding pocket similar to that of rhino-, coxsackie- and poliovirus 3C proteases. We show that compound 1 and rupintrivir are both active against EV-93 in infected cells and inhibit the proteolytic activity of EV-93 3C\n            <jats:sup>pro<\/jats:sup>\n            <jats:italic>in vitro<\/jats:italic>\n            . These results provide a framework for further structure-guided optimization of the tested compounds to produce antiviral drugs against a broad range of EV species.\n          <\/jats:p>","DOI":"10.1128\/jvi.05062-11","type":"journal-article","created":{"date-parts":[[2011,8,11]],"date-time":"2011-08-11T04:01:06Z","timestamp":1313035266000},"page":"10764-10773","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Structural Basis for Antiviral Inhibition of the Main Protease, 3C, from Human Enterovirus 93"],"prefix":"10.1128","volume":"85","author":[{"given":"Lionel","family":"Costenaro","sequence":"first","affiliation":[{"name":"Institute for Research in Biomedicine, Barcelona, Spain"},{"name":"Institut de Biologia Molecular de Barcelona (CSIC), Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuzanna","family":"Kaczmarska","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine, Barcelona, Spain"},{"name":"Institut de Biologia Molecular de Barcelona (CSIC), Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carme","family":"Arnan","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine, Barcelona, Spain"},{"name":"Institut de Biologia Molecular de Barcelona (CSIC), Barcelona, Spain"},{"name":"Present address: Centre de Regulaci\u00f3 Gen\u00f2mica, Dr. Aiguader 88, 08003 Barcelona, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Janowski","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine, Barcelona, Spain"},{"name":"Institut de Biologia Molecular de Barcelona (CSIC), Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Coutard","sequence":"additional","affiliation":[{"name":"Architecture et Fonction des Macromol\u00e9cules Biologiques (UMR 6098 CNRS), Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Sol\u00e0","sequence":"additional","affiliation":[{"name":"Institut de Biologia Molecular de Barcelona (CSIC), Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander E.","family":"Gorbalenya","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hel\u00e9ne","family":"Norder","sequence":"additional","affiliation":[{"name":"Swedish Institute for Disease Control, Solna, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Canard","sequence":"additional","affiliation":[{"name":"Architecture et Fonction des Macromol\u00e9cules Biologiques (UMR 6098 CNRS), Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miquel","family":"Coll","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine, Barcelona, Spain"},{"name":"Institut de Biologia Molecular de Barcelona (CSIC), Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909052925"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf327"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.3.2436-2448.1997"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444906031337"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.2.619-626.2005"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00905-07"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi7010866"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm1097"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444994003112"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.03.007"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.20125"},{"key":"e_1_3_2_13_2","first-page":"165","volume-title":"The picornaviruses","author":"Dougherty J. 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