{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:19:08Z","timestamp":1788373148422,"version":"build-2803163510"},"reference-count":44,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T00:00:00Z","timestamp":1600214400000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccby_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100008316","name":"Baden-W\u00fcrttemberg Stiftung","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100008316","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","award":["2013.0019"],"award-info":[{"award-number":["2013.0019"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Coxsackievirus A24 variant (CVA24v) and human adenovirus 37 (HAdV-37) are leading causative agents of the severe and highly contagious ocular infections acute hemorrhagic conjunctivitis and epidemic keratoconjunctivitis, respectively. Currently, neither vaccines nor antiviral agents are available for treating these diseases, which affect millions of individuals worldwide. CVA24v and HAdV-37 utilize sialic acid as attachment receptors facilitating entry into host cells. Previously, we and others have shown that derivatives based on sialic acid are effective in preventing HAdV-37 binding and infection of cells. Here, we designed and synthesized novel pentavalent sialic acid conjugates and studied their inhibitory effect against CVA24v and HAdV-37 binding and infection of human corneal epithelial cells. The pentavalent conjugates are the first reported inhibitors of CVA24v infection and proved efficient in blocking HAdV-37 binding. Taken together, the pentavalent conjugates presented here form a basis for the development of general inhibitors of these highly contagious ocular pathogens.<\/jats:p>","DOI":"10.1021\/acschembio.0c00446","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T09:20:05Z","timestamp":1598433605000},"page":"2683-2691","source":"Crossref","is-referenced-by-count":20,"title":["Pentavalent Sialic Acid Conjugates Block Coxsackievirus\nA24 Variant and Human Adenovirus Type 37\u2013Viruses That Cause\nHighly Contagious Eye Infections"],"prefix":"10.1021","volume":"15","author":[{"given":"Emil","family":"Johansson","sequence":"first","affiliation":[{"name":"Ume\u00e5 University , , ,","place":["Ume\u00e5, Sweden, SE90187"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5912-8429","authenticated-orcid":true,"given":"Re\u0301mi","family":"Caraballo","sequence":"additional","affiliation":[{"name":"Ume\u00e5 University , , ,","place":["Ume\u00e5, Sweden, SE90187"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitesh","family":"Mistry","sequence":"additional","affiliation":[{"name":"Ume\u00e5 University , , ,","place":["Ume\u00e5, Sweden, SE90185"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Zocher","sequence":"additional","affiliation":[{"name":"University of Tu\u0308bingen , , ,","place":["Tu\u0308bingen, Germany, 72076"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixing","family":"Qian","sequence":"additional","affiliation":[{"name":"Ume\u00e5 University , , ,","place":["Ume\u00e5, Sweden, SE90187"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. David","family":"Andersson","sequence":"additional","affiliation":[{"name":"Ume\u00e5 University , , ,","place":["Ume\u00e5, Sweden, SE90187"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Hurdiss","sequence":"additional","affiliation":[{"name":"Utrecht University , , ,","place":["Utrecht, The Netherlands, 3584CL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naresh","family":"Chandra","sequence":"additional","affiliation":[{"name":"Ume\u00e5 University , , ,","place":["Ume\u00e5, Sweden, SE90185"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Thompson","sequence":"additional","affiliation":[{"name":"Faculty of Biological Sciences, University of Leeds , , ,","place":["Leeds, United Kingdom, LS2 9JT"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Fra\u0308ngsmyr","sequence":"additional","affiliation":[{"name":"Ume\u00e5 University , , ,","place":["Ume\u00e5, Sweden, SE90185"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilo","family":"Stehle","sequence":"additional","affiliation":[{"name":"University of Tu\u0308bingen , , ,","place":["Tu\u0308bingen, Germany, 72076"]},{"name":"Vanderbilt University School of Medicine , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Arnberg","sequence":"additional","affiliation":[{"name":"Ume\u00e5 University , , ,","place":["Ume\u00e5, Sweden, SE90185"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3219-4669","authenticated-orcid":true,"given":"Mikael","family":"Elofsson","sequence":"additional","affiliation":[{"name":"Ume\u00e5 University , , ,","place":["Ume\u00e5, Sweden, SE90187"]},{"name":"Ume\u00e5 University , , ,","place":["Ume\u00e5, Sweden, SE90187"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,8,26]]},"reference":[{"key":"2026090213595764000_cit1","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1001\/jama.2013.280318","article-title":"Conjunctivitis: a systematic review of diagnosis and\ntreatment","volume":"310","author":"Azari","year":"2013","journal-title":"JAMA"},{"key":"2026090213595764000_cit2","first-page":"962","article-title":"New medical\ntreatment for viral conjunctivitis","volume":"109","author":"Uchio","year":"2005","journal-title":"Nippon Ganka\nGakkai Zasshi"},{"key":"2026090213595764000_cit3","doi-asserted-by":"publisher","first-page":"331","DOI":"10.2165\/11585330-000000000-00000","article-title":"Treatment of viral conjunctivitis\nwith antiviral drugs","volume":"71","author":"Skevaki","year":"2011","journal-title":"Drugs"},{"key":"2026090213595764000_cit4","first-page":"637","article-title":"Adenovirus-associated epidemic keratoconjunctivitis\noutbreaks--four states, 2008\u20132010","volume":"62","author":"Centers for Disease Control and Prevention.","year":"2013","journal-title":"MMWR"},{"key":"2026090213595764000_cit5","doi-asserted-by":"publisher","first-page":"45202","DOI":"10.1038\/srep45202","article-title":"Molecular epidemiology\nof acute hemorrhagic\nconjunctivitis caused by coxsackie A type 24 variant in China, 2004\u20132014","volume":"7","author":"Zhang","year":"2017","journal-title":"Sci. Rep."},{"key":"2026090213595764000_cit6","first-page":"511","article-title":"An outbreak of acute\nhaemorrhagic conjunctivitis in Melaka, Malaysia","volume":"44","author":"Ghazali","year":"2003","journal-title":"Singapore Med. J."},{"key":"2026090213595764000_cit7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jcv.2019.01.004","article-title":"Challenges in management\nof epidemic keratoconjunctivitis with emerging recombinant human adenoviruses","volume":"112","author":"Gonzalez","year":"2019","journal-title":"J. Clin. Virol."},{"key":"2026090213595764000_cit8","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1164\/ajrccm.157.2.9608057","article-title":"Multiple cases\nof life-threatening adenovirus pneumonia in a mental health care center","volume":"157","author":"Klinger","year":"1998","journal-title":"Am. J. Respir. Crit. 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Virol."},{"key":"2026090213595764000_cit15","doi-asserted-by":"publisher","first-page":"3061","DOI":"10.1128\/JVI.02470-07","article-title":"Sialic acid\nis a cellular receptor for coxsackievirus A24 variant, an emerging\nvirus with pandemic potential","volume":"82","author":"Nilsson","year":"2008","journal-title":"J. Virol."},{"key":"2026090213595764000_cit16","doi-asserted-by":"publisher","first-page":"7087","DOI":"10.1128\/JVI.79.11.7087-7094.2005","article-title":"Enterovirus 70 binds\nto different glycoconjugates containing alpha2,3-linked sialic acid\non different cell lines","volume":"79","author":"Nokhbeh","year":"2005","journal-title":"J. Virol."},{"key":"2026090213595764000_cit17","doi-asserted-by":"publisher","first-page":"283","DOI":"10.3389\/fcimb.2019.00283","article-title":"Evolutionary\nand structural overview of human picornavirus\ncapsid antibody evasion","volume":"9","author":"Cifuente","year":"2019","journal-title":"Front. Cell. Infect.\nMicrobiol."},{"key":"2026090213595764000_cit18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004401","article-title":"A sialic acid binding\nsite in a human picornavirus","volume":"10","author":"Zocher","year":"2014","journal-title":"PLoS Pathog."},{"key":"2026090213595764000_cit19","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1073\/pnas.1713284115","article-title":"Role\nof enhanced receptor engagement in the evolution of a pandemic acute\nhemorrhagic conjunctivitis virus","volume":"115","author":"Baggen","year":"2018","journal-title":"Proc. Natl.\nAcad. Sci. U. S. A."},{"key":"2026090213595764000_cit20","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1136\/bjo.2009.178772","article-title":"Epidemiological and virological features\nof epidemic keratoconjunctivitis due to new human adenovirus type\n54 in Japan","volume":"95","author":"Kaneko","year":"2011","journal-title":"Br. J. Ophthalmol."},{"key":"2026090213595764000_cit21","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/nm.2267","article-title":"The GD1a glycan is\na cellular receptor for adenoviruses causing epidemic keratoconjunctivitis","volume":"17","author":"Nilsson","year":"2011","journal-title":"Nat. Med."},{"key":"2026090213595764000_cit22","doi-asserted-by":"publisher","first-page":"3897","DOI":"10.1128\/JVI.78.8.3897-3905.2004","article-title":"Membrane cofactor protein is a receptor\nfor adenoviruses associated with epidemic keratoconjunctivitis","volume":"78","author":"Wu","year":"2004","journal-title":"J. Virol."},{"key":"2026090213595764000_cit23","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1128\/JVI.74.1.42-48.2000","article-title":"Adenovirus type 37\nuses sialic acid as a cellular receptor","volume":"74","author":"Arnberg","year":"2000","journal-title":"J.\nVirol."},{"key":"2026090213595764000_cit24","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.molmed.2008.06.002","article-title":"Sialic acids\nin human health and disease","volume":"14","author":"Varki","year":"2008","journal-title":"Trends Mol. Med."},{"key":"2026090213595764000_cit25","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nrd2852","article-title":"From carbohydrate\nleads to glycomimetic drugs","volume":"8","author":"Ernst","year":"2009","journal-title":"Nat. Rev. Drug\nDiscovery"},{"key":"2026090213595764000_cit26","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1021\/cr500303t","article-title":"Glycomimetics\nversus multivalent\nglycoconjugates for the design of high affinity lectin ligands","volume":"115","author":"Cecioni","year":"2015","journal-title":"Chem. Rev."},{"key":"2026090213595764000_cit27","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1021\/cr000418f","article-title":"The cluster glycoside effect","volume":"102","author":"Lundquist","year":"2002","journal-title":"Chem. Rev."},{"key":"2026090213595764000_cit28","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1039\/b901828j","article-title":"Maximising\nmultivalency effects in protein-carbohydrate interactions","volume":"7","author":"Pieters","year":"2009","journal-title":"Org. Biomol. Chem."},{"key":"2026090213595764000_cit29","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/35001095","article-title":"Shiga-like\ntoxins are neutralized by tailored multivalent carbohydrate ligands","volume":"403","author":"Kitov","year":"2000","journal-title":"Nature"},{"key":"2026090213595764000_cit30","doi-asserted-by":"publisher","first-page":"12991","DOI":"10.1021\/ja027584k","article-title":"Solution and crystallographic\nstudies of branched multivalent ligands that Inhibit the receptor-binding\nof cholera toxin","volume":"124","author":"Zhang","year":"2002","journal-title":"J. Am. Chem. Soc."},{"key":"2026090213595764000_cit31","doi-asserted-by":"publisher","first-page":"16271","DOI":"10.1021\/ja038223n","article-title":"On the nature of\nthe multivalency effect: A thermodynamic\nmodel","volume":"125","author":"Kitov","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"2026090213595764000_cit32","doi-asserted-by":"publisher","first-page":"6519","DOI":"10.1002\/anie.201101559","article-title":"A potent trivalent\nsialic acid inhibitor of adenovirus type 37 infection of human corneal\ncells","volume":"50","author":"Spjut","year":"2011","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090213595764000_cit33","doi-asserted-by":"publisher","first-page":"9194","DOI":"10.1039\/C5OB01025J","article-title":"Triazole linker-based\ntrivalent sialic\nacid inhibitors of adenovirus type 37 infection of human corneal epithelial\ncells","volume":"13","author":"Caraballo","year":"2015","journal-title":"Org. Biomol. Chem."},{"key":"2026090213595764000_cit34","doi-asserted-by":"publisher","first-page":"6670","DOI":"10.1021\/jm200545m","article-title":"Molecular wipes: application\nto epidemic keratoconjuctivitis","volume":"54","author":"Aplander","year":"2011","journal-title":"J. Med. Chem."},{"key":"2026090213595764000_cit35","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1039\/B706331H","article-title":"Click multivalent neoglycoconjugates as synthetic activators\nin cell adhesion and stimulation of monocyte\/machrophage cell lines,","volume":"5","author":"Ortega-Mun\u0303oz","year":"2007","journal-title":"Org. Biomol. Chem."},{"key":"2026090213595764000_cit36","doi-asserted-by":"publisher","first-page":"804","DOI":"10.3762\/bjoc.11.90","article-title":"Influence of length and flexibility of spacers on the\nbinding affinity of divalent ligands,","volume":"11","author":"Liese","year":"2015","journal-title":"Beilstein\nJ. Org. Chem."},{"key":"2026090213595764000_cit37","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/0008-6215(89)80054-0","article-title":"Stereoselective\nsynthesis of 2-thioglycosides of N-acetylneuraminic\nacid","volume":"187","author":"Marra","year":"1989","journal-title":"Carbohydr. Res."},{"key":"2026090213595764000_cit38","doi-asserted-by":"publisher","first-page":"3485","DOI":"10.1016\/j.tetlet.2005.03.126","article-title":"Microwave-accelerated\nFischer glycosylation","volume":"46","author":"Bornaghi","year":"2005","journal-title":"Tetrahedron Lett."},{"key":"2026090213595764000_cit39","doi-asserted-by":"publisher","first-page":"7407","DOI":"10.1021\/jo0262412","article-title":"Study of interhalogens\/silver\ntrifluoromethanesulfonate\nas promoter systems for high-yielding sialylations","volume":"67","author":"Meijer","year":"2002","journal-title":"J. Org. Chem."},{"key":"2026090213595764000_cit40","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1006\/jmbi.1999.3483","article-title":"Stabilization of\npoliovirus by capsid-binding antiviral drugs is due to entropic effects","volume":"296","author":"Tsang","year":"2000","journal-title":"J. Mol. Biol."},{"key":"2026090213595764000_cit41","doi-asserted-by":"publisher","first-page":"17457","DOI":"10.1039\/C5NR04139B","article-title":"Hydrophobic pocket targeting probes\nfor enteroviruses","volume":"7","author":"Martikainen","year":"2015","journal-title":"Nanoscale"},{"key":"2026090213595764000_cit42","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s12985-015-0330-4","article-title":"In vitro characterisation\nof a pleconaril\/pirodavir-like compound with potent activity against\nrhinoviruses","volume":"12","author":"Lacroix","year":"2015","journal-title":"Virol. J."},{"key":"2026090213595764000_cit43","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1126\/science.1261962","article-title":"Structure\nand inhibition of EV-D68, a virus that causes respiratory illness\nin children","volume":"347","author":"Liu","year":"2015","journal-title":"Science"},{"key":"2026090213595764000_cit44","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.jviromet.2012.06.014","article-title":"A plate-based\nhigh-throughput assay for virus stability and vaccine formulation","volume":"185","author":"Walter","year":"2012","journal-title":"J. Virol. Methods"}],"container-title":["ACS Chemical Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acschembio.0c00446","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acbcct\/article-pdf\/15\/10\/2683\/66949879\/acschembio.0c00446.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acbcct\/article-pdf\/15\/10\/2683\/66949879\/acschembio.0c00446.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:00:09Z","timestamp":1788372009000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acbcct\/article\/15\/10\/2683\/588834\/Pentavalent-Sialic-Acid-Conjugates-Block"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,26]]},"references-count":44,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,8,26]]},"published-print":{"date-parts":[[2020,10,16]]}},"URL":"https:\/\/doi.org\/10.1021\/acschembio.0c00446","relation":{"has-preprint":[{"id-type":"doi","id":"10.26434\/chemrxiv.12145857.v1","asserted-by":"object"},{"id-type":"doi","id":"10.26434\/chemrxiv.12145857","asserted-by":"object"}]},"ISSN":["1554-8929","1554-8937"],"issn-type":[{"value":"1554-8929","type":"print"},{"value":"1554-8937","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,26]]}}}