{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:15:25Z","timestamp":1760145325515,"version":"build-2065373602"},"reference-count":122,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Najran University","award":["NU\/GP\/MRC\/13\/759","GRD-996"],"award-info":[{"award-number":["NU\/GP\/MRC\/13\/759","GRD-996"]}]},{"name":"Vision Group on Science and Technology, Karnataka, India","award":["NU\/GP\/MRC\/13\/759","GRD-996"],"award-info":[{"award-number":["NU\/GP\/MRC\/13\/759","GRD-996"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The limitations of the current vaccination strategy for the Kyasanur Forest Disease virus (KFDV) underscore the critical need for effective antiviral treatments, highlighting the crucial importance of exploring novel therapeutic approaches through in silico drug design. Kyasanur Forest Disease, caused by KFDV, is a tick-borne disease with a mortality of 3\u20135% and an annual incidence of 400 to 500 cases. In the early stage of infection, the envelope protein plays a crucial role by facilitating host\u2013virus interactions. The objective of this research is to develop effective antivirals targeting the envelope protein to disrupt the virus\u2013host interaction. In line with this, the 3D structure of the envelope protein was modeled and refined through molecular modeling techniques, and subsequently, ligands were designed via de novo design and pharmacophore screening, yielding 12 potential hits followed by ADMET analysis. The top five candidates underwent geometry optimization and molecular docking. Notably, compounds L4 (SA28) and L3 (CNP0247967) are predicted to have significant binding affinities of \u22128.91 and \u22127.58 kcal\/mol, respectively, toward the envelope protein, based on computational models. Both compounds demonstrated stability during 200 ns molecular dynamics simulations, and the MM-GBSA binding free-energy values were \u221285.26 \u00b1 4.63 kcal\/mol and \u221266.60 \u00b1 2.92 kcal\/mol for the envelope protein L3 and L4 complexes, respectively. Based on the computational prediction, it is suggested that both compounds have potential as drug candidates for controlling host\u2013virus interactions by targeting the envelope protein. Further validation through in-vitro assays would complement the findings of the present in silico investigations.<\/jats:p>","DOI":"10.3390\/ph17070884","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T12:28:48Z","timestamp":1720009728000},"page":"884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Computational Exploration of Potential Pharmacological Inhibitors Targeting the Envelope Protein of the Kyasanur Forest Disease Virus"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1111-9456","authenticated-orcid":false,"given":"Sharanappa","family":"Achappa","sequence":"first","affiliation":[{"name":"Department of Biotechnology, KLE Technological University, Hubballi 580031, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nayef Abdulaziz","family":"Aldabaan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Najran University, Najran 66462, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shivalingsarj V.","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, KLE Technological University, Hubballi 580031, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3463-1989","authenticated-orcid":false,"given":"Uday M.","family":"Muddapur","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, KLE Technological University, Hubballi 580031, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim Ahmed","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Najran University, Najran 66462, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4837-3653","authenticated-orcid":false,"given":"Mater H.","family":"Mahnashi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran 66462, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8467-9611","authenticated-orcid":false,"given":"Abdullateef A.","family":"Alshehri","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, P.O. Box 1988, Najran 66462, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2585-2018","authenticated-orcid":false,"given":"Basheerahmed Abdulaziz","family":"Mannasaheb","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5731-7522","authenticated-orcid":false,"given":"Aejaz Abdullatif","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of General Science, Ibn Sina National College for Medical Studies, Jeddah 21418, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.virusres.2011.11.002","article-title":"The generation of a reverse genetics system for Kyasanur Forest Disease Virus and the ability to antagonize the induction of the antiviral state in vitro","volume":"163","author":"Cook","year":"2012","journal-title":"Virus Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"339","DOI":"10.4103\/ijmr.IJMR_532_21","article-title":"Experiences of Indian Council of Medical Research with tick-borne zoonotic infections: Kyasanur Forest disease & Crimean-Congo haemorrhagic fever in India with One Health focus","volume":"153","author":"Mourya","year":"2021","journal-title":"Indian J. 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