{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:27:07Z","timestamp":1787740027375,"version":"build-2784847793"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P41GM136508"],"award-info":[{"award-number":["P41GM136508"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["MCDC\u20102202\u2010002"],"award-info":[{"award-number":["MCDC\u20102202\u2010002"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Advanced Biology"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Paritaprevir is an orally bioavailable, macrocyclic drug used for treating chronic Hepatitis C virus (HCV) infection. Its structures have been elusive to the public until recently when one of the crystal forms is solved by microcrystal electron diffraction (MicroED). In this work, the MicroED structures of two distinct polymorphic crystal forms of paritaprevir are reported from the same experiment. The different polymorphs show conformational changes in the macrocyclic core, as well as the cyclopropyl sulfonamide and methyl pyrazinamide substituents. Molecular docking shows that one of the conformations fits well into the active site pocket of the HCV non\u2010structural 3\/4A (NS3\/4A) serine protease target, and can interact with the pocket and catalytic triad via hydrophobic interactions and hydrogen bonds. These results can provide further insight for optimization of the binding of acyl sulfonamide inhibitors to the HCV NS3\/4A serine protease. In addition, this also demonstrates the opportunity to derive different polymorphs and distinct macrocycle conformations from the same experiments using MicroED.<\/jats:p>","DOI":"10.1002\/adbi.202300570","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T09:45:51Z","timestamp":1708508751000},"source":"Crossref","is-referenced-by-count":15,"title":["Polymorphic Structure Determination of the Macrocyclic Drug Paritaprevir by MicroED"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2797-5161","authenticated-orcid":false,"given":"Guanhong","family":"Bu","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry University of California Los Angeles  615 Charles E. Young Drive South Los Angeles CA 90095 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Danelius","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry University of California Los Angeles  615 Charles E. Young Drive South Los Angeles CA 90095 USA"},{"name":"Howard Hughes Medical Institute University of California Los Angeles  Los Angeles CA 90095 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4617-7605","authenticated-orcid":false,"given":"Lianne H.E.","family":"Wieske","sequence":"additional","affiliation":[{"name":"Department of Chemistry\u2013BMC Uppsala University  Husargatan 3 Uppsala 75237 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9254-4069","authenticated-orcid":false,"given":"Tamir","family":"Gonen","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry University of California Los Angeles  615 Charles E. 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