{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:39:44Z","timestamp":1768505984719,"version":"3.49.0"},"posted":{"date-parts":[[2023,9,6]]},"group-title":"Biochemistry","reference-count":33,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,9,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Meclizine (Antivert, Bonine) is a first-generation 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-drug interactions remained unknown. In this study, we used microcrystal electron diffraction (MicroED) to determine the three-dimensional (3D) crystal structure of meclizine dihydrochloride directly from a seemingly amorphous powder. Two racemic enantiomers (R\/S) were found in the unit cell, which packed as repetitive double layers in the crystal lattice. The packing was made of multiple strong N-H\u00b7\u00b7\u00b7Cl\n                  <jats:sup>-<\/jats:sup>\n                  hydrogen bonding interactions and weak interactions like C-H\u00b7\u00b7\u00b7Cl\n                  <jats:sup>-<\/jats:sup>\n                  and pi-stacking. Molecular docking revealed 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-generation antihistamine) showed the conserved binding sites. This research illustrates the combined use of MicroED and molecular docking in unraveling protein-drug interactions for precision drug design and optimization.\n                <\/jats:p>","DOI":"10.1101\/2023.09.05.556418","type":"posted-content","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:50:12Z","timestamp":1694047812000},"source":"Crossref","is-referenced-by-count":1,"title":["Unraveling the Structure of Meclizine Dihydrochloride with MicroED"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9008-5115","authenticated-orcid":false,"given":"Jieye","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1077-8137","authenticated-orcid":false,"given":"Johan","family":"Unge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9254-4069","authenticated-orcid":false,"given":"Tamir","family":"Gonen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023091201551087000_2023.09.05.556418v1.1","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1111\/bcp.14257","volume":"86","year":"2020","journal-title":"Br. J. Clin. Pharmacol"},{"key":"2023091201551087000_2023.09.05.556418v1.2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1972.00490140033006"},{"key":"2023091201551087000_2023.09.05.556418v1.3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jemermed.2016.09.016","volume":"52","year":"2017","journal-title":"J. Emerg. Med"},{"key":"2023091201551087000_2023.09.05.556418v1.4","doi-asserted-by":"crossref","unstructured":"R. Vardanyan , V. Hruby , in Synthesis of Best-Seller Drugs (Eds.: R. Vardanyan , V. Hruby ), Academic Press, Boston, 2016, pp. 247\u2013263.","DOI":"10.1016\/B978-0-12-411492-0.00016-X"},{"key":"2023091201551087000_2023.09.05.556418v1.5","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1107\/S0567740880007704","volume":"36","year":"1980","journal-title":"Acta Crystallogr. Sect. B"},{"key":"2023091201551087000_2023.09.05.556418v1.6","doi-asserted-by":"crossref","first-page":"o3245","DOI":"10.1107\/S1600536805028357","volume":"61","year":"2005","journal-title":"Acta Crystallogr. Sect. E"},{"key":"2023091201551087000_2023.09.05.556418v1.7","doi-asserted-by":"crossref","first-page":"6634","DOI":"10.1039\/C5TB00676G","volume":"3","year":"2015","journal-title":"J. Mater. Chem. B"},{"key":"2023091201551087000_2023.09.05.556418v1.8","doi-asserted-by":"crossref","first-page":"119840","DOI":"10.1016\/j.ijpharm.2020.119840","volume":"589","year":"2020","journal-title":"Int. J. Pharm"},{"key":"2023091201551087000_2023.09.05.556418v1.9","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1017\/S0885715618000799","volume":"34","year":"2019","journal-title":"Powder Diffr"},{"key":"2023091201551087000_2023.09.05.556418v1.10","doi-asserted-by":"crossref","unstructured":"K. Diederichs , M. Wang , Protein Crystallography: Methods and Protocols 2017, 239\u2013272.","DOI":"10.1007\/978-1-4939-7000-1_10"},{"key":"2023091201551087000_2023.09.05.556418v1.11","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1002\/1521-3773(20010504)40:9<1626::AID-ANIE16260>3.0.CO;2-7","volume":"40","year":"2001","journal-title":"Angew. Chem. Int"},{"key":"2023091201551087000_2023.09.05.556418v1.12","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.01345"},{"key":"2023091201551087000_2023.09.05.556418v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2014.03.004"},{"key":"2023091201551087000_2023.09.05.556418v1.14","unstructured":"D. P. Karothu , Z. Alhaddad , C. R. G\u00f6b , C. J. Sch\u00fcrmann , R. B\u00fccker , P. Naumov , Angew. Chem. Int. Ed. 2023, e202303761."},{"key":"2023091201551087000_2023.09.05.556418v1.15","unstructured":"S. Kane , ClinCalc DrugStats Database, 2020, 20."},{"key":"2023091201551087000_2023.09.05.556418v1.16","doi-asserted-by":"crossref","unstructured":"R. Vardanyan , V. Hruby , Synthesis of essential drugs 2006, 219\u2013235.","DOI":"10.1016\/B978-044452166-8\/50016-9"},{"key":"2023091201551087000_2023.09.05.556418v1.17","doi-asserted-by":"crossref","first-page":"219","DOI":"10.4103\/0019-5154.110832","volume":"58","year":"2013","journal-title":"Indian J. Dermatol"},{"key":"2023091201551087000_2023.09.05.556418v1.18","unstructured":"H. L. Haas , O. A. Sergeeva , O. Selbach , Physiol. Rev. 2008."},{"key":"2023091201551087000_2023.09.05.556418v1.19","doi-asserted-by":"publisher","DOI":"10.1177\/0269881113516201"},{"key":"2023091201551087000_2023.09.05.556418v1.20","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1358\/dot.2004.40.5.850489","volume":"40","year":"2004","journal-title":"Drugs Today (Barc)"},{"key":"2023091201551087000_2023.09.05.556418v1.21","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1021\/acscentsci.8b00760","volume":"4","year":"2018","journal-title":"ACS Cent. Sci"},{"key":"2023091201551087000_2023.09.05.556418v1.22","doi-asserted-by":"publisher","DOI":"10.1107\/S2052252519010583"},{"key":"2023091201551087000_2023.09.05.556418v1.23","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909047337"},{"key":"2023091201551087000_2023.09.05.556418v1.24","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909047374"},{"key":"2023091201551087000_2023.09.05.556418v1.25","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053273314026370","volume":"71","year":"2015","journal-title":"Acta Crystallogr. Sect. A"},{"key":"2023091201551087000_2023.09.05.556418v1.26","doi-asserted-by":"publisher","DOI":"10.1107\/S0108767307043930"},{"key":"2023091201551087000_2023.09.05.556418v1.27","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1021\/cg034083h","volume":"3","year":"2003","journal-title":"Cryst. Growth Des"},{"key":"2023091201551087000_2023.09.05.556418v1.28","doi-asserted-by":"publisher","DOI":"10.1039\/c2sc20045g"},{"key":"2023091201551087000_2023.09.05.556418v1.29","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1038\/s41467-021-22427-2","volume":"12","year":"2021","journal-title":"Nat. Commun"},{"key":"2023091201551087000_2023.09.05.556418v1.30","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.1c00203"},{"key":"2023091201551087000_2023.09.05.556418v1.31","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"2023091201551087000_2023.09.05.556418v1.32","doi-asserted-by":"publisher","DOI":"10.2174\/092986708785747625"},{"key":"2023091201551087000_2023.09.05.556418v1.33","doi-asserted-by":"publisher","DOI":"10.1124\/mol.61.2.391"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.09.05.556418","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:11:08Z","timestamp":1768453868000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.09.05.556418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,6]]},"references-count":33,"URL":"https:\/\/doi.org\/10.1101\/2023.09.05.556418","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1002\/advs.202306435","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,9,6]]},"subtype":"preprint"}}