Identification and nanoformulation study of novel 1,2,3-triazole clickamers as potential antivirals against H5N1 and SARS-CoV-2

We have prepared and characterized a series of 1,2,3-triazole clickamers using the standard click chemistry approach. The compounds were obtained in high yields (80-90%) by the reaction of diazides with 2-ethynylpyrazine or ethynylbenzene catalyzed by Cu(I) ions via in situ reduction of CuSO₄. Spectroscopic analyses confirmed the chemical structures of the synthesized compounds. The antiviral evaluation revealed significant efficacy of compounds 8, 9, and 10 against SARS-CoV-2, while compounds 7 and 9 showed strong activity against H5N1. Compound 8, selected for further study, was encapsulated in ethyl cellulose nanoparticles (EC-NPs) with a size of 87.27 ± 0.9 nm. The nanoformulation showed negative zeta potential, ensuring stability and improved cell penetration. The release of compound 8 from the EC-NPs was controlled and sustained over time, reaching 38.72% after six hours and 88.16% after 12 hours. The nanoformulation showed significant antiviral activity and reduced the IC₅₀ value of compound 8 from 32.26 µM to 15.40 µM in the case of antiviral screening against SARS-CoV-2. Molecular docking experiments showed strong interactions between compound 8 and key proteins of SARS-CoV-2. The 1,2,3-triazoles developed in this study offer a significant contribution to the field of antiviral therapeutics and pave the way for promising clinical applications.