{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T20:30:30Z","timestamp":1776976230709,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,12,3]],"date-time":"2023-12-03T00:00:00Z","timestamp":1701561600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,12,3]],"date-time":"2023-12-03T00:00:00Z","timestamp":1701561600000},"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":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Meclizine (Antivert, Bonine) is a first\u2010generation H1 antihistamine used in the treatment of motion sickness and vertigo. Despite its wide medical use for over 70 years, its crystal structure and the details of protein\u2010drug interactions remained unknown. Single\u2010crystal X\u2010ray diffraction (SC\u2010XRD) is previously unsuccessful for meclizine. Today, microcrystal electron diffraction (MicroED) enables the analysis of nano\u2010 or micro\u2010sized crystals that are merely a billionth the size needed for SC\u2010XRD directly from seemingly amorphous powder. In this study, MicroED to determine the 3D crystal structure of meclizine dihydrochloride is used. Two racemic enantiomers (R\/S) are found in the unit cell, which is packed as repetitive double layers in the crystal lattice. The packing is made of multiple strong N\u2010H\u2010Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    hydrogen bonding interactions and weak interactions like C\u2010H\u2010Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    and pi\u2010stacking. Molecular docking reveals the binding mechanism of meclizine to the histamine H1 receptor. A comparison of the docking complexes between histamine H1 receptor and meclizine or levocetirizine (a second\u2010generation antihistamine) shows the conserved binding sites. This research illustrates the combined use of MicroED and molecular docking in unraveling elusive drug structures and protein\u2010drug interactions for precision drug design and optimization.\n                  <\/jats:p>","DOI":"10.1002\/advs.202306435","type":"journal-article","created":{"date-parts":[[2023,12,3]],"date-time":"2023-12-03T22:28:14Z","timestamp":1701642494000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Unraveling the Structure of Meclizine Dihydrochloride with MicroED"],"prefix":"10.1002","volume":"11","author":[{"given":"Jieye","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry University of California  615 Charles E. Young Drive South Los Angeles CA 90095 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Unge","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry University of California  615 Charles E. Young Drive South Los Angeles CA 90095 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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  615 Charles E. Young Drive South Los Angeles CA 90095 USA"},{"name":"Department of Physiology University of California  615 Charles E. Young Drive South Los Angeles CA 90095 USA"},{"name":"Howard Hughes Medical Institute University of California  Los Angeles CA 90095 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,3]]},"reference":[{"key":"e_1_2_5_1_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14257"},{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1972.00490140033006"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jemermed.2016.09.016"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-411492-0.00016-X"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0567740880007704"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600536805028357"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5TB00676G"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.119840"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0885715618000799"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7000-1_10"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3773(20010504)40:9<1626::AID-ANIE16260>3.0.CO;2-7"},{"key":"e_1_2_5_12_1","volume":"20","author":"Kane S.","year":"2020","journal-title":"ClinCalc DrugStats Database"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40853-2"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c13733"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.01345"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2014.03.004"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202303761"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-044452166-8\/50016-9"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019-5154.110832"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00043.2007"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881113516201"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1358\/dot.2004.40.5.850489"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.8b00760"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2052252519010583"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909047337"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909047374"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2053273314026370"},{"key":"e_1_2_5_28_1","unstructured":"Crystallographic Information File (CIF) of Meclizine dihydrochloride is deposited in Cambridge Crystallographic Data Center (CCDC) and the number is 2293443."},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2053229614024218"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/cg034083h"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2sc20045g"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22427-2"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.1c00203"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986708785747625"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.61.2.391"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202306435","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202306435","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T20:28:31Z","timestamp":1759782511000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202306435"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,3]]},"references-count":36,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/advs.202306435"],"URL":"https:\/\/doi.org\/10.1002\/advs.202306435","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.09.05.556418","asserted-by":"object"}]},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,3]]},"assertion":[{"value":"2023-09-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2306435"}}