{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:30:56Z","timestamp":1790652656833,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T00:00:00Z","timestamp":1529971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003323","name":"Agence Nationale de Recherches sur le Sida et les H\u00e9patites Virales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003323","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003323","name":"Agence Nationale de Recherches sur le Sida et les H\u00e9patites Virales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003323","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Although members of the\n            <jats:named-content content-type=\"genus-species\">Flaviviridae<\/jats:named-content>\n            display high incidence, morbidity, and mortality rates, the development of specific antiviral drugs for each virus is unlikely. Cyclophilins, a family of host peptidyl-prolyl\n            <jats:italic>cis-trans<\/jats:italic>\n            isomerases (PPIases), play a pivotal role in the life cycles of many viruses and therefore represent an attractive target for broad-spectrum antiviral development. We report here the pangenotypic anti-hepatitis C virus (HCV) activity of a small-molecule cyclophilin inhibitor (SMCypI). Mechanistic and modeling studies revealed that the SMCypI bound to cyclophilin A in competition with cyclosporine (CsA), inhibited its PPIase activity, and disrupted the CypA-nonstructural protein 5A (NS5A) interaction. Resistance selection showed that the lead SMCypI hardly selected amino acid substitutions conferring low-level or no resistance\n            <jats:italic>in vitro<\/jats:italic>\n            . Interestingly, the SMCypI selected D320E and Y321H substitutions, located in domain II of the NS5A protein. These substitutions were previously associated with low-level resistance to cyclophilin inhibitors such as alisporivir. Finally, the SMCypI inhibited the replication of other members of the\n            <jats:named-content content-type=\"genus-species\">Flaviviridae<\/jats:named-content>\n            family with higher 50% effective concentrations (EC\n            <jats:sub>50<\/jats:sub>\n            s) than for HCV. Thus, because of its chemical plasticity and simplicity of synthesis, our new family of SMCypIs represents a promising new class of drugs with the potential for broad-spectrum anti-\n            <jats:named-content content-type=\"genus-species\">Flaviviridae<\/jats:named-content>\n            activity as well as an invaluable tool to explore the role of cyclophilins in viral life cycles.\n          <\/jats:p>","DOI":"10.1128\/aac.00126-18","type":"journal-article","created":{"date-parts":[[2018,5,9]],"date-time":"2018-05-09T09:18:38Z","timestamp":1525857518000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Characterization of the Anti-Hepatitis C Virus Activity of New Nonpeptidic Small-Molecule Cyclophilin Inhibitors with the Potential for Broad Anti-Flaviviridae Activity"],"prefix":"10.1128","volume":"62","author":[{"given":"Quentin","family":"Nevers","sequence":"first","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale, INSERM U955 Team 18, H\u00f4pital Henri Mondor, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale, INSERM U955 Team 18, H\u00f4pital Henri Mondor, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazim","family":"Ahnou","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale, INSERM U955 Team 18, H\u00f4pital Henri Mondor, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"},{"name":"National Reference Center for Viral Hepatitis B, C, and D, Department of Virology, H\u00f4pital Henri Mondor, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Donati","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale, INSERM U955 Team 18, H\u00f4pital Henri Mondor, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"},{"name":"National Reference Center for Viral Hepatitis B, C, and D, Department of Virology, H\u00f4pital Henri Mondor, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rozenn","family":"Brillet","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale, INSERM U955 Team 18, H\u00f4pital Henri Mondor, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Softic","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale, INSERM U955 Team 18, H\u00f4pital Henri Mondor, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Chazal","sequence":"additional","affiliation":[{"name":"Unit\u00e9 G\u00e9nomique Virale et Vaccination, CNRS UMR 3569, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nolwenn","family":"Jouvenet","sequence":"additional","affiliation":[{"name":"Unit\u00e9 G\u00e9nomique Virale et Vaccination, CNRS UMR 3569, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slim","family":"Fourati","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale, INSERM U955 Team 18, H\u00f4pital Henri Mondor, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"},{"name":"National Reference Center for Viral Hepatitis B, C, and D, Department of Virology, H\u00f4pital Henri Mondor, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Baudesson","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale, INSERM U955 Team 18, H\u00f4pital Henri Mondor, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Bruscella","sequence":"additional","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale, INSERM U955 Team 18, H\u00f4pital Henri Mondor, Universit\u00e9 Paris-Est, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Gelin","sequence":"additional","affiliation":[{"name":"Centre de Biochimie Structurale, INSERM, CNRS, Universit\u00e9 de Montpellier, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Guichou","sequence":"additional","affiliation":[{"name":"Centre de Biochimie Structurale, 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