{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:23:49Z","timestamp":1787660629269,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Alphaviruses transmitted by mosquitoes represent an expanding global health concern, yet no specific antiviral agents are currently available for clinical use. Trehalose\u2010derived glycolipids have emerged as promising host\u2010modulating compounds with antiviral potential, but their relevance to alphavirus infection has remained largely unexplored. Here, we investigated the antiviral properties and underlying mechanism of trehalose 6\u2010monolaurate (TML) against Sindbis virus (SINV), a representative Old World alphavirus. In cell\u2010based infection models, TML demonstrated strong antiviral efficacy with favorable selectivity, substantially outperforming the structurally related analog trehalose 6\u2010monooleate. Exposure to TML led to a concentration\u2010dependent reduction in intracellular viral RNA synthesis, viral protein accumulation, and release of infectious progeny across distinct cell types. Kinetic and mechanistic analyses indicated that TML exerts its antiviral activity predominantly after viral entry, while exerting limited influence on virion integrity, cellular attachment, or internalization. Global transcriptomic analysis revealed that TML counterbalances SINV\u2010driven host gene expression programs, particularly those involving immediate\u2010early transcriptional regulators and pathways linked to Wnt signaling, cellular metabolism, and biosynthetic processes. Network\u2010based interrogation further highlighted EGR1\u2010associated transcriptional hubs as central targets of TML\u2010mediated modulation. Together, these results establish TML as a host\u2010directed inhibitor acting at post\u2010entry stages of alphavirus replication and underscore its potential as a lead scaffold for the development of therapeutics against mosquito\u2010borne RNA viruses.<\/jats:p>","DOI":"10.1002\/jmv.71094","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:54:31Z","timestamp":1786082071000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Mechanism of Monolaurate Derived Glycolipids Inhibit Sindbis Virus Replication and Release"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2128-2046","authenticated-orcid":false,"given":"Jeng\u2010Wei","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Bioscience and Biotechnology National Taiwan Ocean University Keelung Taiwan"},{"name":"Biotech Research and Innovation Centre University of Copenhagen Copenhagen Denmark"},{"name":"The Finsen Laboratory, Rigshospitalet\/National University Hospital, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Helal","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Experimental and Molecular Psychiatry Translational Neuropsychiatry Unit, Aarhus University Aarhus Denmark"},{"name":"National Institute of Oceanography and Fisheries Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan\u2010Chiun","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Life Science, National Taiwan Normal University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8998-4098","authenticated-orcid":false,"given":"Chia\u2010Hsin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine Tri\u2010Service General Hospital, National Defense Medical University Taipei Taiwan"},{"name":"Graduate Institute of Life Sciences National Defense Medical University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1291-8946","authenticated-orcid":false,"given":"Feng\u2010Cheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences National Defense Medical University Taipei Taiwan"},{"name":"Department of Internal Medicine, Rheumatology\/Immunology and Allergy Tri\u2010Service General Hospital, National Defense Medical University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting\u2010Chun","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences National Defense Medical University Taipei Taiwan"},{"name":"School of Pharmacy, National Defense Medical University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Zhe","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, National Defense Medical University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3931-2302","authenticated-orcid":false,"given":"Yi\u2010Jung","family":"Ho","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences National Defense Medical University Taipei Taiwan"},{"name":"School of Pharmacy, National Defense Medical University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007213"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0188-4409(02)00378-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-016-0443-5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508391103"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2015.04.016"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2023.2300452"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.1876"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181843d94"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/vbz.2007.0152"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2016691117"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365540701586996"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000389"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1985.34.194"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.7.1.89"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.00959"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e328303220b"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES2014.19.28.20854"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.spid.2006.04.009"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.9.6697-6705.1997"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1955.4.844"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.21649"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.me.33.020182.000335"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.22.12750"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13040603"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.61.12.3809-3819.1987"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)80049-4"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1997.tb01013.x"},{"issue":"5","key":"e_1_2_9_29_1","first-page":"503","article-title":"Basis of Neurovirulence in Sindbis Virus Encephalomyelitis of Mice","volume":"58","author":"Jackson A. C.","year":"1988","journal-title":"Laboratory Investigation: A Journal of Technical Methods and Pathology"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.11.5352-5356.2000"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.13.6156-6161.2000"},{"issue":"4","key":"e_1_2_9_32_1","first-page":"418","article-title":"The Pathogenesis of Spinal Cord Involvement in the Encephalomyelitis of Mice Caused by Neuroadapted Sindbis Virus Infection","volume":"56","author":"Jackson A. C.","year":"1987","journal-title":"Laboratory Investigation: A Journal of Technical Methods and Pathology"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1418966111"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00173-15"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.6b00686"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2018.04.005"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02441"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2011.05.003"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.22112"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00402"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.11.8142-8147.1996"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0133511"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2018.10.005"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2016.10.003"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.07.157"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2021.105188"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/v11121112"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-6-109"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-8-163"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.483"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.1020220"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/v14061210"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087768"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.139527"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.71094","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmv.71094","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.71094","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:40:01Z","timestamp":1787658001000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.71094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":53,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/jmv.71094"],"URL":"https:\/\/doi.org\/10.1002\/jmv.71094","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"value":"0146-6615","type":"print"},{"value":"1096-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2026-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71094"}}