Antiviral activity of newly synthesized pyrazole derivatives against Newcastle disease virus
Ahmed El‐Sewedy, Alaa R. I. Morsy, Eman A. El‐Bordany, Naglaa F. H. Mahmoud, Safwa Z. Mohamed, Sayed K. Ramadan
Abstract
Newcastle disease virus (NDV) is a highly contagious poultry disease that affects the respiratory, nervous, and digestive systems, causing significant losses to the poultry industry. 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 6 and thiazolidinedione derivative 9 achieved complete (100%) protection against NDV with 0% mortality, while the pyrazolopyrimidine derivative 7 provided 95% protection. Additionally, tetrazine 4 and chalcone 11 conferred 85% and 80% protection, respectively. Molecular docking simulation targeting immune receptor TLR4 protein (PDB ID: 3MU3) revealed that compound 6 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 9 formed two hydrogen bonds with THR 122 and exhibited hydrophobic interaction with TYR 117, whereas compound 7 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.