{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T18:30:02Z","timestamp":1767378602887,"version":"3.48.0"},"reference-count":81,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100016230","name":"Steven and Alexandra Cohen Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI080615, R01AI116620, P01AI138949"],"award-info":[{"award-number":["R01AI080615, R01AI116620, P01AI138949"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008510","name":"University of Maryland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["ZIA TR000355-04"],"award-info":[{"award-number":["ZIA TR000355-04"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    , one of the most prevalent tick-borne pathogens, can cause a complex and multisystem illness called Lyme disease, where there has been an unmet need for novel therapeutic or preventive strategies. We previously identified an essential protein-protein interaction (PPI) event in\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    involving two unique proteins, BB0323 and BB0238; herein, we show that this PPI is indispensable for long-term borrelial survival in mammals and explore its potential as a novel target for small molecule therapeutics. Using X-ray crystallography, we solved the structure of the BB0238-BB0323 complex and identified the hotspot residues that form the biomolecular PPI interface area of ~1000 square \u00c5ngstroms. We then performed quantitative high-throughput drug screens of 62,740 diverse small molecules utilizing an amplified luminescent proximity homogeneous assay linked immunosorbent assay (AlphaLISA). Following a comprehensive pipeline to confirm small molecule hits, we short-listed three distinct PPI inhibitors of BB0238-BB0323. One of these inhibitors, called lomibuvir (VX-222, VCH-222), displayed robust PPI inhibition inside\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    cells and was shown to affect pathogen persistence in a tick-borne murine model of Lyme disease. Our study highlights targeted PPI disruption as a new therapeutic strategy against\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    and may foster future antimicrobial discovery efforts to resolve clinical complications associated with Lyme disease.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013805","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T18:27:46Z","timestamp":1767378466000},"page":"e1013805","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting of interaction between BB0323-BB0238 informs new paradigms in Lyme disease therapeutics"],"prefix":"10.1371","volume":"22","author":[{"given":"Sandhya","family":"Bista","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalvis","family":"Brangulis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bibek","family":"Bhattachan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelby D.","family":"Foor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael H.","family":"Ronzetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sankalp","family":"Jain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenna","family":"Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jothy Lachumy","family":"Subramanion","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chrysoula","family":"Kitsou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vipin S.","family":"Rana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ganesha","family":"Rai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexey V.","family":"Zakharov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Simeonov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bolormaa","family":"Baljinnyam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7504-4628","authenticated-orcid":true,"given":"Utpal","family":"Pal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,1,2]]},"reference":[{"issue":"3","key":"ppat.1013805.ref001","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.idc.2022.03.004","article-title":"Epidemiology of Lyme Disease","volume":"36","author":"P Mead","year":"2022","journal-title":"Infect Dis Clin North Am"},{"key":"ppat.1013805.ref002","unstructured":"CDC, C. f. 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