{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T09:08:16Z","timestamp":1788599296879,"version":"build-2803163510"},"reference-count":34,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013772","name":"SENS Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["1DP1 OD029517"],"award-info":[{"award-number":["1DP1 OD029517"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000923","name":"Silicon Valley Community Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005492","name":"Stanford University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005492","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Maxwell Biosciences, Inc"},{"name":"New York State Biodefense Commercialization Fund"},{"name":"Truchard Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Herpes simplex virus type-1 (HSV-1) infections cause recurrent oral lesions and are the primary cause of infectious blindness and genital lesions in developed countries. HSV-1 can also lead to life-threatening infections in immunocompromised individuals. Currently, the primary class of antiviral therapeutics for HSV-1 treatment are nucleoside analogues such as acyclovir. However, these therapeutics are only partially effective and are subject to development of resistance. Thus, the development of new, effective antiviral agents, which can be used topically to inactivate HSV-1, is a necessity. We have recently demonstrated the potent antiviral activity of a family of biomimetic compounds. These \u2018peptoid\u2019 (N-substituted glycine) oligomers mimic the structure and activity of antimicrobial peptides like LL-37, while being highly resistant to proteases. Antiviral peptoids rapidly inactivate HSV-1 in vitro by disruption of the viral envelope, likely through interaction with the lipid phosphatidylserine on the outer membrane leaflet. To test the in vivo activity of these peptoids, we optimized a lip treatment model of HSV-1 infection. We demonstrate that delivery of a clinical isolate of HSV-1, strain 294.1, onto scarified lips of BALB\/c mice led to reproducible lesions within 5 days. Treatment of these lesions on day 2 post infection with increasing concentrations of an antiviral peptoid resulted in a dose-dependent inhibition of lesion formation, comparable to acyclovir cream, and the host defense peptide LL-37. The same dose-dependence was observed when quantifying viral DNA from both the lip and the trigeminal ganglion by qPCR. The results demonstrate the ability of these peptoids to be developed as topical antiviral agents to prevent herpes labialis infections caused by HSV-1.<\/jats:p>","DOI":"10.1021\/acsinfecdis.6c00224","type":"journal-article","created":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T18:48:58Z","timestamp":1783277338000},"page":"2703-2712","source":"Crossref","is-referenced-by-count":1,"title":["<i>In Vivo<\/i>\n                    Activity of Antimicrobial\nPeptoid Oligomers against HSV-1 in a\nMouse Model of Herpes Labialis"],"prefix":"10.1021","volume":"12","author":[{"given":"Erika L.","family":"Figgins","sequence":"first","affiliation":[{"name":"University of Louisville School of Dentistry , , , ,","place":["Louisville, Kentucky, United States, 40202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3765-5791","authenticated-orcid":true,"given":"Denny","family":"Gao","sequence":"additional","affiliation":[{"name":"University of Louisville School of Dentistry , , , ,","place":["Louisville, Kentucky, United States, 40202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6422-7720","authenticated-orcid":true,"given":"Lisa K.","family":"Ryan","sequence":"additional","affiliation":[{"name":"University of Louisville School of Dentistry , , , ,","place":["Louisville, Kentucky, United States, 40202"]},{"name":"University of Louisville , , , ,","place":["Louisville, Kentucky, United States, 40202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9169-7410","authenticated-orcid":true,"given":"Jennifer S.","family":"Lin","sequence":"additional","affiliation":[{"name":"Stanford University Schools of Medicine and Engineering , , , ,","place":["Stanford, California, United States, 94305"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7643-4508","authenticated-orcid":true,"given":"Natalia","family":"Molchanova","sequence":"additional","affiliation":[{"name":"Stanford University Schools of Medicine and Engineering , , , ,","place":["Stanford, California, United States, 94305"]},{"name":"Lawrence Berkeley National Laboratory , , , ,","place":["Berkeley, California, United States, 94720"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M.","family":"Rudnic","sequence":"additional","affiliation":[{"name":"Maxwell Biosciences , , ,","place":["Austin, Texas, United States, 78738"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheetal","family":"Vali","sequence":"additional","affiliation":[{"name":"Maxwell Biosciences , , ,","place":["Austin, Texas, United States, 78738"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S.","family":"Shumway","sequence":"additional","affiliation":[{"name":"University of Louisville School of Dentistry , , , ,","place":["Louisville, Kentucky, United States, 40202"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent","family":"Kirshenbaum","sequence":"additional","affiliation":[{"name":"New York University , , , ,","place":["New York, New York, United States, 10003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0735-6873","authenticated-orcid":true,"given":"Annelise E.","family":"Barron","sequence":"additional","affiliation":[{"name":"Stanford University Schools of Medicine and Engineering , , , ,","place":["Stanford, California, United States, 94305"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3596-9773","authenticated-orcid":true,"given":"Gill","family":"Diamond","sequence":"additional","affiliation":[{"name":"University of Louisville School of Dentistry , , , ,","place":["Louisville, Kentucky, United States, 40202"]},{"name":"University of Louisville , , , ,","place":["Louisville, Kentucky, United States, 40202"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"issue":"4","key":"2026081410070504800_cit1","doi-asserted-by":"publisher","first-page":"304","DOI":"10.3390\/ph14040304","article-title":"Potent\nAntiviral Activity against HSV-1 and SARS-CoV-2\nby Antimicrobial Peptoids","volume":"14","author":"Diamond","year":"2021","journal-title":"Pharmaceuticals (Basel)"},{"issue":"5","key":"2026081410070504800_cit2","doi-asserted-by":"publisher","first-page":"315","DOI":"10.2471\/BLT.19.237149","article-title":"Herpes simplex virus: global infection\nprevalence and incidence estimates, 2016","volume":"98","author":"James","year":"2020","journal-title":"Bull.\nWorld Health Organ"},{"issue":"4","key":"2026081410070504800_cit3","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1542\/pir.30.4.119","article-title":"Herpes\nsimplex","volume":"30","author":"Chayavichitsilp","year":"2009","journal-title":"Pediatr Rev."},{"issue":"3","key":"2026081410070504800_cit4","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1111\/j.1574-6976.2011.00320.x","article-title":"The molecular basis of herpes simplex\nvirus latency","volume":"36","author":"Nicoll","year":"2012","journal-title":"FEMS Microbiol Rev."},{"issue":"11","key":"2026081410070504800_cit5","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1056\/NEJM199209103271108","article-title":"Acyclovir:\na decade later","volume":"327","author":"Wood","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"2026081410070504800_cit6","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1111\/odi.14635","article-title":"Management of oral herpes simplex\nvirus infections: The problem of resistance. A narrative review","volume":"30","author":"Piperi","year":"2024","journal-title":"Oral Dis."},{"issue":"9","key":"2026081410070504800_cit7","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.2174\/0929867326666190805151654","article-title":"Antiviral Activities\nof Human Host Defense Peptides","volume":"27","author":"Brice","year":"2020","journal-title":"Curr. Med. Chem."},{"issue":"1","key":"2026081410070504800_cit8","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.cellimm.2012.11.009","article-title":"A comprehensive summary\nof LL-37, the factotum human cathelicidin peptide","volume":"280","author":"Vandamme","year":"2012","journal-title":"Cell Immunol"},{"key":"2026081410070504800_cit9","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.antiviral.2018.07.025","article-title":"LL-37 disrupts\nthe Kaposi\u2019s\nsarcoma-associated herpesvirus envelope and inhibits infection in\noral epithelial cells","volume":"158","author":"Brice","year":"2018","journal-title":"Antiviral Res."},{"issue":"8","key":"2026081410070504800_cit10","doi-asserted-by":"publisher","first-page":"2794","DOI":"10.1073\/pnas.0708254105","article-title":"Peptoids that mimic\nthe structure, function, and mechanism of helical antimicrobial peptides","volume":"105","author":"Chongsiriwatana","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"3","key":"2026081410070504800_cit11","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1021\/acsinfecdis.1c00536","article-title":"Self-Assembly\nof Antimicrobial Peptoids Impacts Their Biological Effects on ESKAPE\nBacterial Pathogens","volume":"8","author":"Nielsen","year":"2022","journal-title":"ACS Infect Dis"},{"issue":"8","key":"2026081410070504800_cit12","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1021\/acsinfecdis.3c00063","article-title":"Peptidomimetic\nOligomers Targeting Membrane Phosphatidylserine Exhibit Broad Antiviral\nActivity","volume":"9","author":"Tate","year":"2023","journal-title":"ACS Infect Dis"},{"key":"2026081410070504800_cit13","unstructured":"Barron, A. E.; Czyzewski, A. M.; Dohm, M. T.; Miller, T. M.; Zuckermann, R. N.; Patch, J. A.; Chongsiriwatana, N. P.\n          Selective poly-N-substituted glycine antibiotics.\nUnited States US-8445632-B2, 2013."},{"issue":"47","key":"2026081410070504800_cit14","doi-asserted-by":"publisher","first-page":"32637","DOI":"10.1074\/jbc.M805533200","article-title":"Structures\nof human host defense cathelicidin LL-37 and its smallest antimicrobial\npeptide KR-12 in lipid micelles","volume":"283","author":"Wang","year":"2008","journal-title":"J. Biol. Chem."},{"issue":"1","key":"2026081410070504800_cit15","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1128\/AAC.01080-10","article-title":"Short alkylated peptoid mimics of antimicrobial lipopeptides","volume":"55","author":"Chongsiriwatana","year":"2011","journal-title":"Antimicrob. 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Infect Dis"},{"key":"2026081410070504800_cit19","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/2042-4280-3-4","article-title":"The effect\nof mouse strain on herpes\nsimplex virus type 1 (HSV-1) infection of the central nervous system\n(CNS)","volume":"3","author":"Kastrukoff","year":"2012","journal-title":"Herpesviridae"},{"issue":"4","key":"2026081410070504800_cit20","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.ijantimicag.2018.06.019","article-title":"beta-Carboline\nderivatives as novel antivirals for herpes simplex virus","volume":"52","author":"Gonzalez","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"issue":"1","key":"2026081410070504800_cit21","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/s12985-024-02384-0","article-title":"Harmol used\nfor the treatment of herpes simplex virus induced keratitis","volume":"21","author":"Xu","year":"2024","journal-title":"Virol J."},{"issue":"1","key":"2026081410070504800_cit22","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/s13365-014-0302-2","article-title":"Animal\nmodels of\nherpes simplex virus immunity and pathogenesis","volume":"21","author":"Kollias","year":"2015","journal-title":"J. Neurovirol"},{"issue":"2","key":"2026081410070504800_cit23","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/S0166-0934(98)00107-4","article-title":"Expression\nof the enhanced green\nfluorescent protein by herpes simplex virus type 1 (HSV-1) as an in\nvitro or in vivo marker for virus entry and replication","volume":"75","author":"Foster","year":"1998","journal-title":"J. Virol Methods"},{"key":"2026081410070504800_cit24","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1189\/jlb.0209079","article-title":"Modulation\nof human beta-defensin-1 (hBD-1) in plasmacytoid dendritic cells (PDC),\nmonocytes, and epithelial cells by influenza virus, Herpes simplex\nvirus, and Sendai virus and its possible role in innate immunity","volume":"90","author":"Ryan","year":"2011","journal-title":"J. Leukoc Biol."},{"issue":"2","key":"2026081410070504800_cit25","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1006\/viro.1998.9447","article-title":"A herpes simplex\nvirus DNA polymerase mutation that specifically attenuates neurovirulence\nin mice","volume":"252","author":"Pelosi","year":"1998","journal-title":"Virology"},{"issue":"1","key":"2026081410070504800_cit26","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1128\/jvi.70.1.264-271.1996","article-title":"Inflammatory\ninfiltration of the\ntrigeminal ganglion after herpes simplex virus type 1 corneal infection","volume":"70","author":"Liu","year":"1996","journal-title":"J. Virol."},{"issue":"10","key":"2026081410070504800_cit27","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00783-23","article-title":"A fur plucking model\nto study herpes\nsimplex virus reactivation and recurrent disease","volume":"9","author":"Philip","year":"2024","journal-title":"mSphere"},{"issue":"2","key":"2026081410070504800_cit28","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/S0022-3565(25)12947-9","article-title":"Pharmacologic\ncharacterization\nof CHIR 2279, an N-substituted glycine peptoid with high-affinity\nbinding for alpha 1-adrenoceptors","volume":"277","author":"Gibbons","year":"1996","journal-title":"J. Pharmacol\nExp Ther"},{"key":"2026081410070504800_cit29","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1002\/ddr.430350105","article-title":"Comparison of the proteolytic susceptibilites\nof homologous L-amino acid, D-amino acid, and N-substituted glycine\npeptide and peptoid oligomers","volume":"35","author":"Miller","year":"1995","journal-title":"Drug Dev. Res."},{"issue":"5","key":"2026081410070504800_cit30","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1021\/bc300091d","article-title":"In vivo biodistribution\nand small animal PET of (64)Cu-labeled antimicrobial peptoids","volume":"23","author":"Seo","year":"2012","journal-title":"Bioconjug Chem."},{"key":"2026081410070504800_cit31","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/aic.11402","article-title":"Protein and peptide\nbiomimicry: Gold-mining inspiration\nfrom Nature\u2019s ingenuity","volume":"54","author":"Czyzewski","year":"2008","journal-title":"AIChE J."},{"key":"2026081410070504800_cit32","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/bs.mie.2021.04.022","article-title":"Submonomer\nsynthesis of sequence defined peptoids with diverse side-chains","volume":"656","author":"Connolly","year":"2021","journal-title":"Methods Enzymol."},{"issue":"1806","key":"2026081410070504800_cit33","doi-asserted-by":"publisher","first-page":"20150293","DOI":"10.1098\/rspb.2015.0293","article-title":"Insect antimicrobial peptides show potentiating\nfunctional interactions against Gram-negative bacteria","volume":"282","author":"Rahnamaeian","year":"2015","journal-title":"Proc. Biol. Sci."},{"issue":"4","key":"2026081410070504800_cit34","doi-asserted-by":"publisher","first-page":"303","DOI":"10.4103\/0976-500X.119726","article-title":"How to calculate sample size in animal studies?","volume":"4","author":"Charan","year":"2013","journal-title":"J. Pharmacol Pharmacother"}],"container-title":["ACS Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsinfecdis.6c00224","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/12\/8\/2703\/65776192\/acsinfecdis.6c00224.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/12\/8\/2703\/65776192\/acsinfecdis.6c00224.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T14:23:17Z","timestamp":1786717397000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article\/12\/8\/2703\/5200031\/In-Vivo-Activity-of-Antimicrobial-Peptoid"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,5]]},"references-count":34,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,7,5]]},"published-print":{"date-parts":[[2026,8,14]]}},"URL":"https:\/\/doi.org\/10.1021\/acsinfecdis.6c00224","relation":{},"ISSN":["2373-8227"],"issn-type":[{"value":"2373-8227","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,5]]}}}