{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:58:55Z","timestamp":1788998335036,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T00:00:00Z","timestamp":1751673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"governments of Bangladesh"},{"name":"Global Affairs Canada"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The Chikungunya virus (CHIKV) continues to pose a significant global health challenge due to the absence of effective antiviral treatments and limited vaccine availability. This study employed a comprehensive in silico workflow, incorporating high-throughput virtual screening, binding free-energy calculations, ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis, and 200 ns molecular dynamics (MD) simulations, to identify new inhibitors targeting the E1\u2013E2 glycoprotein complex, crucial for CHIKV entry and membrane fusion. Four promising candidates were identified from a library of 20,000 compounds, with CID 136801451 showing the most potent binding (docking score: \u221210.227; \u0394G_bind: \u221251.53 kcal\/mol). The top four compounds exhibited favorable ADMET profiles, meeting nearly all criteria. MD simulations confirmed stable binding and strong interactions between CID 136801451 and the E1\u2013E2 complex, evidenced by consistently low RMSD values. These findings highlight CID 136801451 as a promising CHIKV entry inhibitor, warranting further in vitro and in vivo evaluation to advance the development of effective anti-CHIKV therapeutics.<\/jats:p>","DOI":"10.3390\/ijms26136480","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T08:58:23Z","timestamp":1751878703000},"page":"6480","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Potent Inhibition of Chikungunya Virus Entry by a Pyrazole\u2013Benzene Derivative: A Computational Study Targeting the E1\u2013E2 Glycoprotein Complex"],"prefix":"10.3390","volume":"26","author":[{"given":"Md. Mohibur","family":"Rahman","sequence":"first","affiliation":[{"name":"One Health Laboratory, Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4173-5110","authenticated-orcid":false,"given":"Md. Belayet Hasan","family":"Limon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7270-5411","authenticated-orcid":false,"given":"Tanvir Ahmed","family":"Saikat","sequence":"additional","affiliation":[{"name":"One Health Laboratory, Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poulomi","family":"Saha","sequence":"additional","affiliation":[{"name":"One Health Laboratory, Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1912-126X","authenticated-orcid":false,"given":"Abdul Hadi","family":"Nahid","sequence":"additional","affiliation":[{"name":"One Health Laboratory, Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0064-1812","authenticated-orcid":false,"given":"Mohammad Mamun","family":"Alam","sequence":"additional","affiliation":[{"name":"One Health Laboratory, Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4103-4835","authenticated-orcid":false,"given":"Mohammed Ziaur","family":"Rahman","sequence":"additional","affiliation":[{"name":"One Health Laboratory, Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nrmicro2368","article-title":"Biology and pathogenesis of chikungunya virus","volume":"8","author":"Schwartz","year":"2010","journal-title":"Nat. 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