{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:01:38Z","timestamp":1789646498896,"version":"4.0.0"},"reference-count":57,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012768","name":"Long Island University","doi-asserted-by":"publisher","award":["36524"],"award-info":[{"award-number":["36524"]}],"id":[{"id":"10.13039\/100012768","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012768","name":"Long Island University","doi-asserted-by":"publisher","award":["40262"],"award-info":[{"award-number":["40262"]}],"id":[{"id":"10.13039\/100012768","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012768","name":"Long Island University","doi-asserted-by":"publisher","award":["NI24AHDRXXXXG066"],"award-info":[{"award-number":["NI24AHDRXXXXG066"]}],"id":[{"id":"10.13039\/100012768","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Helaine Lerner and Joan Rechnitz","award":["36524"],"award-info":[{"award-number":["36524"]}]},{"name":"Helaine Lerner and Joan Rechnitz","award":["40262"],"award-info":[{"award-number":["40262"]}]},{"name":"Helaine Lerner and Joan Rechnitz","award":["NI24AHDRXXXXG066"],"award-info":[{"award-number":["NI24AHDRXXXXG066"]}]},{"name":"USDA-NIFA Animal Health and Disease Research","award":["36524"],"award-info":[{"award-number":["36524"]}]},{"name":"USDA-NIFA Animal Health and Disease Research","award":["40262"],"award-info":[{"award-number":["40262"]}]},{"name":"USDA-NIFA Animal Health and Disease Research","award":["NI24AHDRXXXXG066"],"award-info":[{"award-number":["NI24AHDRXXXXG066"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>(1) Background: The highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b is an emerging threat that poses a great risk to the poultry industry. A few human cases have been linked to the infection with this clade in many parts of the world, including the USA. Unfortunately, there are no specific vaccines or antiviral drugs that could help prevent and treat the infection caused by this virus in birds. Our major objective is to identify\/repurpose some (novel\/known) antiviral compounds that may inhibit viral replication by targeting some key viral proteins. (2) Methods: We used state-of-the-art machine learning tools such as molecular docking and MD-simulation methods from Biovia Discovery Studio (v24.1.0.321712). The key target proteins such as hemagglutinin (HA), neuraminidase (NA), Matrix-2 protein (M2), and the cap-binding domain of PB2 (PB2\/CBD) homology models were validated through structural assessment via DOPE scores, Ramachandran plots, and Verify-3D metrics, ensuring reliable structural representations, confirming their reliability for subsequent in silico approaches. These approaches include molecular docking followed by molecular dynamics simulation for 50 nanoseconds (ns), highlighting the structural stability and compactness of the docked complexes. (3) Results: Molecular docking revealed strong binding affinities for both sofosbuvir and GS441524, particularly with the NA and PB2\/CBD protein targets. Among them, GS441524 exhibited superior interaction scores and a greater number of hydrogen bonds with key functional residues of NA and PB2\/CBD. The MM-GBSA binding free energy calculations further supported these findings, as GS441524 displayed more favorable binding energies compared to several known standard inhibitors, including F0045S for HA, Zanamivir for NA, Rimantadine and Amantadine for M2, and PB2-39 for PB2\/CBD. Additionally, 50 ns molecular dynamics simulations highlighted the structural stability and compactness of the GS441524-PB2\/CBD complex, further supporting its potential as a promising antiviral candidate. Furthermore, hydrogen bond monitor analysis over the 50 ns simulation confirmed persistent and specific interactions between the ligand and proteins, suggesting that GS441524 may effectively inhibit the NA, and PB2\/CBD might potentially disrupt PB2-mediated RNA synthesis. (4) Conclusions: Our findings are consistent with previous evidence supporting the antiviral activity of certain nucleoside analog inhibitors, including GS441524, against various coronaviruses. These results further support the potential repurposing of GS441524 as a promising therapeutic candidate against H5N1 avian influenza clade 2.3.4.4b. However, further functional studies are required to validate these in silico predictions and support the inhibitory action of GS441524 against the targeted proteins of H5N1, specifically clade 2.3.4.4b.<\/jats:p>","DOI":"10.3390\/v17070972","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T15:19:31Z","timestamp":1752247171000},"page":"972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repurposing of Some Nucleoside Analogs Targeting Some Key Proteins of the Avian H5N1 Clade 2.3.4.4b to Combat the Circulating HPAI in Birds: An In Silico Approach"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1107-7428","authenticated-orcid":false,"given":"Mohd Yasir","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Computer Science, College of Digital Engineering and Artificial Intelligence, Long Island University, Brooklyn, NY 11201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abid Ullah","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, Long Island University, 720 Northern Boulevard, Brookville, NY 11548, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nithyadevi","family":"Duraisamy","sequence":"additional","affiliation":[{"name":"Department of Computer Science, College of Digital Engineering and Artificial Intelligence, Long Island University, Brooklyn, NY 11201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Cherkaoui","sequence":"additional","affiliation":[{"name":"Department of Computer Science, College of Digital Engineering and Artificial Intelligence, Long Island University, Brooklyn, NY 11201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1663-5820","authenticated-orcid":false,"given":"Maged Gomaa","family":"Hemida","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, Long Island University, 720 Northern Boulevard, Brookville, NY 11548, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dou, D., Revol, R., Ostbye, H., Wang, H., and Daniels, R. 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