{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:27:46Z","timestamp":1778642866398,"version":"3.51.4"},"reference-count":45,"publisher":"Portland Press Ltd.","issue":"6","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,3,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Semen-derived amyloid fibrils, comprising SEVI (semen-derived enhancer of viral infection) fibrils and SEM1 fibrils, could remarkably enhance HIV-1 sexual transmission and thus are potential targets for the development of an effective microbicide. Previously, we found that ADS-J1, apart from being an HIV-1 entry inhibitor, could also potently inhibit seminal amyloid fibrillization and block fibril-mediated enhancement of viral infection. However, the remodeling effects of ADS-J1 on mature seminal fibrils were unexplored. Herein, we investigated the capacity of ADS-J1 to disassemble seminal fibrils and the potential mode of action by applying several biophysical and biochemical measurements, combined with molecular dynamic (MD) simulations. We found that ADS-J1 effectively remodeled SEVI, SEM186\u2013107 fibrils and endogenous seminal fibrils. Unlike epigallocatechin gallate (EGCG), a universal amyloid fibril breaker, ADS-J1 disaggregated SEVI fibrils into monomeric peptides, which was independent of oxidation reaction. MD simulations revealed that ADS-J1 displayed strong binding potency to the full-length PAP248\u2013286 via electrostatic interactions, hydrophobic interactions and hydrogen bonds. ADS-J1 might initially bind to the fibrillar surface and then occupy the amyloid core, which eventually lead to fibril disassembly. Furthermore, the binding of ADS-J1 with PAP248\u2013286 might induce conformational changes of PAP248\u2013286. Disassembled PAP248\u2013286 might not be favorable to re-aggregate into fibrils. ADS-J1 also exerts abilities to remodel a panel of amyloid fibrils, including A\u03b21\u201342, hIAPP1\u201337 and EP2 fibrils. ADS-J1 displays promising potential to be a combination microbicide and an effective lead-product to treat amyloidogenic diseases.<\/jats:p>","DOI":"10.1042\/bcj20180886","type":"journal-article","created":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T12:36:24Z","timestamp":1552653384000},"page":"1021-1035","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["ADS-J1 disaggregates semen-derived amyloid fibrils"],"prefix":"10.1042","volume":"476","author":[{"given":"Jinqing","family":"Li","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zichao","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengjie","family":"Qiu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjuan","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaofeng","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Qi","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yurong","family":"Qiu","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuefeng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences (CAS) Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, CAS, Guangzhou 510515, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuwen","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7078-4689","authenticated-orcid":false,"given":"Suiyi","family":"Tan","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2019,3,29]]},"reference":[{"key":"2021112217552836000_BCJ-2018-0886C1","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1146\/annurev-med-050911-163701","article-title":"Systemic and topical drugs for the prevention of HIV infection: antiretroviral pre-exposure prophylaxis","volume":"64","year":"2013","journal-title":"Annu. Rev. Med."},{"key":"2021112217552836000_BCJ-2018-0886C2","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.jconrel.2014.09.013","article-title":"Formulation and delivery of anti-HIV rectal microbicides: advances and challenges","volume":"194","year":"2014","journal-title":"J. Control. Release"},{"key":"2021112217552836000_BCJ-2018-0886C3","doi-asserted-by":"publisher","first-page":"5123","DOI":"10.1128\/AAC.00385-15","article-title":"ADS-J1 inhibits semen-derived amyloid fibril formation and blocks fibril-mediated enhancement of HIV-1 infection","volume":"59","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"2021112217552836000_BCJ-2018-0886C4","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1093\/infdis\/jiw131","article-title":"Seminal HIV-1 RNA detection in heterosexual African men initiating antiretroviral therapy","volume":"214","year":"2016","journal-title":"J. Infect. Dis."},{"key":"2021112217552836000_BCJ-2018-0886C5","doi-asserted-by":"publisher","first-page":"262ra157","DOI":"10.1126\/scitranslmed.3009634","article-title":"Semen enhances HIV infectivity and impairs the antiviral efficacy of microbicides","volume":"6","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"2021112217552836000_BCJ-2018-0886C6","doi-asserted-by":"publisher","first-page":"3508","DOI":"10.1038\/ncomms4508","article-title":"Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen","volume":"5","year":"2014","journal-title":"Nat. Commun."},{"key":"2021112217552836000_BCJ-2018-0886C7","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1016\/j.cell.2007.10.014","article-title":"Semen-derived amyloid fibrils drastically enhance HIV infection","volume":"131","year":"2007","journal-title":"Cell"},{"key":"2021112217552836000_BCJ-2018-0886C8","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.chom.2011.10.010","article-title":"Peptides released by physiological cleavage of semen coagulum proteins form amyloids that enhance HIV infection","volume":"10","year":"2011","journal-title":"Cell Host Microbe"},{"key":"2021112217552836000_BCJ-2018-0886C9","doi-asserted-by":"publisher","first-page":"7221","DOI":"10.1128\/JVI.00269-14","article-title":"Liquefaction of semen generates and later degrades a conserved semenogelin peptide that enhances HIV infection","volume":"88","year":"2014","journal-title":"J. Virol."},{"key":"2021112217552836000_BCJ-2018-0886C10","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1128\/JVI.01366-08","article-title":"The cationic properties of SEVI underlie its ability to enhance human immunodeficiency virus infection","volume":"83","year":"2009","journal-title":"J. Virol."},{"key":"2021112217552836000_BCJ-2018-0886C11","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3390\/biology1010058","article-title":"The surprising role of amyloid fibrils in HIV infection","volume":"1","year":"2012","journal-title":"Biology"},{"key":"2021112217552836000_BCJ-2018-0886C12","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1021\/acs.accounts.7b00154","article-title":"Natural seminal amyloids as targets for development of synthetic inhibitors of HIV transmission","volume":"50","year":"2017","journal-title":"Acc. Chem. Res."},{"key":"2021112217552836000_BCJ-2018-0886C13","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1016\/j.bbamem.2013.12.022","article-title":"ADS-J1 inhibits HIV-1 infection and membrane fusion by targeting the highly conserved pocket in the gp41 NHR-trimer","volume":"1838","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"2021112217552836000_BCJ-2018-0886C14","doi-asserted-by":"publisher","first-page":"4487","DOI":"10.1128\/AAC.00359-10","article-title":"ADS-J1 inhibits HIV-1 entry by interacting with gp120 and does not block fusion-active gp41 core formation","volume":"54","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"2021112217552836000_BCJ-2018-0886C15","doi-asserted-by":"publisher","first-page":"e59777","DOI":"10.1371\/journal.pone.0059777","article-title":"Polyanionic candidate microbicides accelerate the formation of semen-derived amyloid fibrils to enhance HIV-1 infection","volume":"8","year":"2013","journal-title":"PLoS ONE"},{"key":"2021112217552836000_BCJ-2018-0886C16","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1021\/acschembio.5b00146","article-title":"Molecular tweezers inhibit islet amyloid polypeptide assembly and toxicity by a new mechanism","volume":"10","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"2021112217552836000_BCJ-2018-0886C17","doi-asserted-by":"publisher","first-page":"17972","DOI":"10.1021\/ja908170s","article-title":"NMR structure in a membrane environment reveals putative amyloidogenic regions of the SEVI precursor peptide PAP(248-286)","volume":"131","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"2021112217552836000_BCJ-2018-0886C18","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","year":"2010","journal-title":"J. Comput. Chem."},{"key":"2021112217552836000_BCJ-2018-0886C19","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1093\/bioinformatics\/btt055","article-title":"GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit","volume":"29","year":"2013","journal-title":"Bioinformatics"},{"key":"2021112217552836000_BCJ-2018-0886C20","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1002\/jcc.540040211","article-title":"CHARMM: a program for macromolecular energy, minimization, and dynamics calculations","volume":"4","year":"1983","journal-title":"J. Comput. Chem."},{"key":"2021112217552836000_BCJ-2018-0886C21","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water","volume":"79","year":"1983","journal-title":"J. Chem. Phys."},{"key":"2021112217552836000_BCJ-2018-0886C22","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1002\/(SICI)1096-987X(199709)18:12&lt;1463::AID-JCC4&gt;3.0.CO;2-H","article-title":"LINCS: a linear constraint solver for molecular simulations","volume":"18","year":"1997","journal-title":"J. Comput. Chem."},{"key":"2021112217552836000_BCJ-2018-0886C23","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: an N log(N) method for Ewald sums in large systems","volume":"98","year":"1993","journal-title":"J. Chem. Phys."},{"key":"2021112217552836000_BCJ-2018-0886C24","doi-asserted-by":"publisher","first-page":"2981","DOI":"10.1093\/bioinformatics\/btu426","article-title":"YASARA View \u2013 molecular graphics for all devices \u2013 from smartphones to workstations","volume":"30","year":"2014","journal-title":"Bioinformatics"},{"key":"2021112217552836000_BCJ-2018-0886C25","doi-asserted-by":"publisher","first-page":"35176","DOI":"10.1074\/jbc.M102223200","article-title":"Amyloid \u03b2-protein oligomerization: prenucleation interactions revealed by photo-induced cross-linking of unmodified proteins","volume":"276","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2021112217552836000_BCJ-2018-0886C26","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/nprot.2006.4","article-title":"Tricine-SDS-PAGE","volume":"1","year":"2006","journal-title":"Nat. Protoc."},{"key":"2021112217552836000_BCJ-2018-0886C27","doi-asserted-by":"publisher","first-page":"7503","DOI":"10.1021\/ja3115696","article-title":"Toward the molecular mechanism(s) by which EGCG treatment remodels mature amyloid fibrils","volume":"135","year":"2013","journal-title":"J. Am. Chem. Soc."},{"key":"2021112217552836000_BCJ-2018-0886C28","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1210\/endo.141.2.7378","article-title":"Amylin: a novel action in the brain to reduce body weight","volume":"141","year":"2000","journal-title":"Endocrinology"},{"key":"2021112217552836000_BCJ-2018-0886C29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2016\/2798269","article-title":"Islet amyloid polypeptide: structure, function, and pathophysiology","volume":"2016","year":"2016","journal-title":"J. Diabetes Res."},{"key":"2021112217552836000_BCJ-2018-0886C30","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1016\/j.febslet.2014.03.016","article-title":"Peptides derived from HIV-1 gp120 co-receptor binding domain form amyloid fibrils and enhance HIV-1 infection","volume":"588","year":"2014","journal-title":"FEBS Lett."},{"key":"2021112217552836000_BCJ-2018-0886C31","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S0166-0934(99)00041-5","article-title":"A screening assay for antiviral compounds targeted to the HIV-1 gp41 core structure using a conformation-specific monoclonal antibody","volume":"80","year":"1999","journal-title":"J. Virol. Methods"},{"key":"2021112217552836000_BCJ-2018-0886C32","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1016\/j.bmc.2015.02.041","article-title":"\u03b2-Sheet interfering molecules acting against \u03b2-amyloid aggregation and fibrillogenesis","volume":"23","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"2021112217552836000_BCJ-2018-0886C33","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1021\/acschemneuro.6b00154","article-title":"Modulation of amyloid \u03b2-protein (A\u03b2) assembly by homologous C-terminal fragments as a strategy for inhibiting a\u03b2 toxicity","volume":"7","year":"2016","journal-title":"ACS Chem. Neurosci."},{"key":"2021112217552836000_BCJ-2018-0886C34","doi-asserted-by":"publisher","first-page":"40095","DOI":"10.1038\/srep40095","article-title":"Disaggregation of amylin aggregate by novel conformationally restricted aminobenzoic acid containing \u03b1\/\u03b2 and \u03b1\/\u03b3 hybrid peptidomimetics","volume":"7","year":"2017","journal-title":"Sci. Rep."},{"key":"2021112217552836000_BCJ-2018-0886C35","doi-asserted-by":"publisher","first-page":"e05397","DOI":"10.7554\/eLife.05397","article-title":"A molecular tweezer antagonizes seminal amyloids and HIV infection","volume":"4","year":"2015","journal-title":"eLife"},{"key":"2021112217552836000_BCJ-2018-0886C36","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1021\/cn200133x","article-title":"Comparison of three amyloid assembly inhibitors: the sugar scyllo-inositol, the polyphenol epigallocatechin gallate, and the molecular tweezer CLR01","volume":"3","year":"2012","journal-title":"ACS Chem. Neurosci."},{"key":"2021112217552836000_BCJ-2018-0886C37","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1007\/s13311-012-0105-1","article-title":"A novel \u2018molecular tweezer\u2019 inhibitor of \u03b1-synuclein neurotoxicity in vitro and in vivo","volume":"9","year":"2012","journal-title":"Neurotherapeutics"},{"key":"2021112217552836000_BCJ-2018-0886C38","doi-asserted-by":"publisher","first-page":"9478","DOI":"10.1021\/jf0519055","article-title":"Stability of tea polyphenol (\u2212)-epigallocatechin-3-gallate and formation of dimers and epimers under common experimental conditions","volume":"53","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"2021112217552836000_BCJ-2018-0886C39","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1080\/13543776.2016.1203419","article-title":"Therapeutic effects of EGCG: a patent review","volume":"26","year":"2016","journal-title":"Expert Opin. Ther. Pat."},{"key":"2021112217552836000_BCJ-2018-0886C40","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.2147\/IJN.S29341","article-title":"Encapsulated nanoepigallocatechin-3-gallate and elemental selenium nanoparticles as paradigms for nanochemoprevention","volume":"7","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"2021112217552836000_BCJ-2018-0886C41","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/1472-6882-14-115","article-title":"Liver toxicity during temozolomide chemotherapy caused by Chinese herbs","volume":"14","year":"2014","journal-title":"BMC Complement. Altern. Med."},{"key":"2021112217552836000_BCJ-2018-0886C42","doi-asserted-by":"publisher","first-page":"15270","DOI":"10.1038\/srep15270","article-title":"EGCG antagonizes Bortezomib cytotoxicity in prostate cancer cells by an autophagic mechanism","volume":"5","year":"2015","journal-title":"Sci. Rep."},{"key":"2021112217552836000_BCJ-2018-0886C43","doi-asserted-by":"publisher","first-page":"5927","DOI":"10.1182\/blood-2008-07-171389","article-title":"Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors","volume":"113","year":"2009","journal-title":"Blood"},{"key":"2021112217552836000_BCJ-2018-0886C44","doi-asserted-by":"publisher","first-page":"3487","DOI":"10.1073\/pnas.0915166107","article-title":"Identifying the amylome, proteins capable of forming amyloid-like fibrils","volume":"107","year":"2010","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021112217552836000_BCJ-2018-0886C45","doi-asserted-by":"publisher","first-page":"18223","DOI":"10.1021\/ja1069882","article-title":"Mechanistic studies of peptide self-assembly: transient \u03b1-helices to stable \u03b2-sheets","volume":"132","year":"2010","journal-title":"J. Am. Chem. Soc."}],"container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/476\/6\/1021\/861566\/bcj-2018-0886.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/476\/6\/1021\/861566\/bcj-2018-0886.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T21:23:28Z","timestamp":1637616208000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/476\/6\/1021\/219518\/ADS-J1-disaggregates-semen-derived-amyloid-fibrils"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,29]]},"references-count":45,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,3,29]]}},"URL":"https:\/\/doi.org\/10.1042\/bcj20180886","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/292342","asserted-by":"object"}]},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,29]]}}}