{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:14:43Z","timestamp":1790612083966,"version":"4.1.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["2710008770, KK-2513-01 and 1711202880"],"award-info":[{"award-number":["2710008770, KK-2513-01 and 1711202880"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Leptospirosis is a zoonotic disease caused by\n                      <jats:italic>Leptospira interrogans<\/jats:italic>\n                      and represents a major public health and veterinary concern. The persistence of the pathogen is closely associated with biofilm formation, yet targeted therapeutics are currently unavailable. The GroEL chaperonin, a conserved protein involved in biofilm formation and immunogenicity, was investigated as a potential therapeutic target.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A structure-based virtual screening approach was performed using a library of 543,503 natural compounds from the Life Chemicals database. Top-ranked ligands were evaluated using molecular docking and physicochemical and pharmacokinetic property analyses. Density functional theory calculations were performed to assess electronic stability, followed by molecular dynamics simulations to evaluate ligand\u2013protein complex stability. Principal component analysis and MM-PBSA binding free energy calculations were subsequently applied to characterize conformational dynamics and binding affinity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Five compounds (F3385-2019, F1243-0200, F3139-0927, F2801-0179, and F1864-0208) exhibited strong binding affinities toward GroEL, with docking energies ranging from \u221210.34 to \u22128.26 kcal\/mol. All shortlisted compounds complied with Lipinski\u2019s Rule of Five and demonstrated favorable pharmacokinetic properties. Molecular dynamics simulations and MM-PBSA analyses indicated stable ligand\u2013protein interactions. Among the candidates, F1864\u20130208 and F1243\u20130200 emerged as the most stable and promising leads, whereas the remaining compounds showed moderate inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      This study provides computational evidence supporting GroEL as a viable drug target in\n                      <jats:italic>L. interrogans<\/jats:italic>\n                      . The identified natural compounds may represent promising scaffolds for the development of novel anti-leptospiral agents. Further\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies are required to validate their therapeutic efficacy and safety.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1733096","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T06:31:32Z","timestamp":1770013892000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Computational identification of natural inhibitors targeting GroEL in Leptospira interrogans: an integrative virtual screening and molecular dynamics approach"],"prefix":"10.3389","volume":"15","author":[{"given":"Guneswar","family":"Sethi","sequence":"first","affiliation":[{"name":"Center for Large Animals Convergence Research, Korea Institute of Toxicology","place":["Jeongeup-si, Jeollabuk-do, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sthitaprajna","family":"Sahoo","sequence":"additional","affiliation":[{"name":"Department of Agricultural Convergence Technology, Jeonbuk National University","place":["Jeonju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Cheol","family":"Han","sequence":"additional","affiliation":[{"name":"Center for Large Animals Convergence Research, Korea Institute of Toxicology","place":["Jeongeup-si, Jeollabuk-do, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghyun","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Agricultural Convergence Technology, Jeonbuk National University","place":["Jeonju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Ho","family":"Hwang","sequence":"additional","affiliation":[{"name":"Division of Advanced Predictive Research, Center for Bio-Signal Research, Korea Institute of Toxicology","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3127","DOI":"10.1016\/j.bmcl.2016.04.089","article-title":"GroEL\/ES inhibitors as potential antibiotics","volume":"26","author":"Abdeen","year":"2016","journal-title":"Bioorg Med. 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