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Pyrazole-based scaffolds had significant potential as antiviral agents targeting various pathogens. Thus, a series of 4-substituted pyrazole derivatives were synthesized by reacting 5-chloro-4-formyl-3-methyl-1-phenylpyrazole with some nitrogen and carbon-based nucleophiles. The antiviral efficacy of these compounds was evaluated against NDV by assessing their ability to inhibit virus-induced haemagglutination. Notably, hydrazone\n                    <jats:bold>6<\/jats:bold>\n                    and thiazolidinedione derivative\n                    <jats:bold>9<\/jats:bold>\n                    achieved complete (100%) protection against NDV with 0% mortality, while the pyrazolopyrimidine derivative\n                    <jats:bold>7<\/jats:bold>\n                    provided 95% protection. Additionally, tetrazine\n                    <jats:bold>4<\/jats:bold>\n                    and chalcone\n                    <jats:bold>11<\/jats:bold>\n                    conferred 85% and 80% protection, respectively. Molecular docking simulation targeting immune receptor TLR4 protein (PDB ID: 3MU3) revealed that compound\n                    <jats:bold>6<\/jats:bold>\n                    achieved the highest docking score, surpassing both the reference drug (amantadine) and the co-crystallized ligand (LP4), primarily through hydrophobic interactions with PHE 46 residue. Compound\n                    <jats:bold>9<\/jats:bold>\n                    formed two hydrogen bonds with THR 122 and exhibited hydrophobic interaction with TYR 117, whereas compound\n                    <jats:bold>7<\/jats:bold>\n                    interacted hydrophobically with THR 122. Pharmacokinetic modeling using the BOILED-Egg model indicated that some compounds are likely to cross the blood-brain barrier (yellow region), while others remain in the white area. Impressively, the compounds also demonstrated desirable drug-likeness profiles. These findings suggest that the synthesized compounds hold promise as potent antiviral candidates.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-03495-6","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T13:52:23Z","timestamp":1748440343000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Antiviral activity of newly synthesized pyrazole derivatives against Newcastle disease virus"],"prefix":"10.1038","volume":"15","author":[{"given":"Ahmed","family":"El-Sewedy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa R. 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