{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:17:26Z","timestamp":1785403046493,"version":"3.56.0"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"crossref","award":["ORF-2026-628"],"award-info":[{"award-number":["ORF-2026-628"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"crossref"}]},{"award":["ORF-2026-628"],"award-info":[{"award-number":["ORF-2026-628"]}],"id":[{"id":"https:\/\/ror.org\/02f81g417","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2026R342"],"award-info":[{"award-number":["PNURSP2026R342"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PNURSP2026R342"],"award-info":[{"award-number":["PNURSP2026R342"]}],"id":[{"id":"https:\/\/ror.org\/05b0cyh02","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ebola virus disease remains one of the most serious viral infections with no approved small-molecule treatments. The Ebola virus glycoprotein (EBOV-GP), which enables the virus\u2019s entry to host cells, is a promising target for drug discovery. In this study, a multistage computer-aided drug discovery approach was used to identify new specific EBOV-GP inhibitors. A reliable QSAR model was built using 55 terpenoid derivatives. This model was able to predict the activity of newly designed compounds with good accuracy and validated statistical metrics (Rtr2\u00a0= 0.70; Rext2 = 0.73). It was subsequently applied to screen over 15,500 newly generated compounds from three lead molecules by fragment-based design tools. Predicted activity, binding affinity toward EBOV-GP, and good ADMET drug-like properties prioritized the eleven most promising hits. Through 150 ns molecular dynamics simulations, these compounds remained stable in the EBOV-GP binding site. Further binding free energy analysis (MM\/PBSA) showed strong binding affinities, especially for the compounds L-60, L-832, M-1618, and L-1366. This study showed how combining QSAR, fragment-based design, docking, ADMET, and molecular dynamics could help in identifying potent and safe small molecules against the EBOV-GP. The top compounds are ready for further experimental and in vitro biological testing.<\/jats:p>","DOI":"10.3390\/ijms27072987","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T13:57:34Z","timestamp":1774447054000},"page":"2987","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["QSAR-Guided and Fragment-Based Drug Design of Monoterpenoid Inhibitors Targeting Ebola Virus Glycoprotein"],"prefix":"10.3390","volume":"27","author":[{"given":"Nouhaila","family":"Ait Lahcen","sequence":"first","affiliation":[{"name":"Molecular Chemistry Laboratory, Faculty of Sciences Semlalia, Cadi Ayyad University, UCA, Marrakech 40000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0670-5709","authenticated-orcid":false,"given":"Wissal","family":"Liman","sequence":"additional","affiliation":[{"name":"Bioinformatics Laboratory, College of Computing, University Mohammed VI Polytechnic, Benguerir 43150, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad","family":"Zekri","sequence":"additional","affiliation":[{"name":"Molecular Chemistry Laboratory, Faculty of Sciences Semlalia, Cadi Ayyad University, UCA, Marrakech 40000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnane","family":"Ait Lahcen","sequence":"additional","affiliation":[{"name":"Molecular Chemistry Laboratory, Faculty of Sciences Semlalia, Cadi Ayyad University, UCA, Marrakech 40000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1042-8126","authenticated-orcid":false,"given":"Ashwag S.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0483-8113","authenticated-orcid":false,"given":"Mohammed M.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Delaite","sequence":"additional","affiliation":[{"name":"Laboratoire de Photochimie et d\u2019Ing\u00e9nierie Macromol\u00e9culaires (LPIM), Ecole Nationale Sup\u00e9rieure de Chimie de Mulhouse, Universit\u00e9 de Haute-Alsace, 68100 Mulhouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7921-8587","authenticated-orcid":false,"given":"Mohamed","family":"Maatallah","sequence":"additional","affiliation":[{"name":"Molecular Chemistry Laboratory, Faculty of Sciences Semlalia, Cadi Ayyad University, UCA, Marrakech 40000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Driss","family":"Cherqaoui","sequence":"additional","affiliation":[{"name":"Molecular Chemistry Laboratory, Faculty of Sciences Semlalia, Cadi Ayyad University, UCA, Marrakech 40000, Morocco"},{"name":"Sustainable Materials Research Center (SUSMAT-RC), University of Mohammed VI Polytechnic, Benguerir 43150, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nature07082","article-title":"Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human Survivor","volume":"454","author":"Lee","year":"2008","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1038\/s41401-023-01055-0","article-title":"Inhibiting the Transcription and Replication of Ebola Viruses by Disrupting the Nucleoprotein and VP30 Protein Interaction with Small Molecules","volume":"44","author":"Ma","year":"2023","journal-title":"Acta Pharmacol. 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