BACKGROUND: Emergence of new pathogenic viruses along with adaptive potential of RNA viruses has become a major public health concern. Hence it becomes even more important to explore and evaluate the antiviral properties of nanocomposites which is an ever-evolving field of medical biology. METHODS: In this study, series of metal/metal oxide (Ag/NiO : NiO, AN-5%, AN-10% and AN-15%) and ternary metal oxide nanocomposites (Ag2O/NiO/ZnO : N/Z, A/N/Z-1, A/N/Z-2 and A/N/Z-3) have been synthesized and characterized. Cellular uptake of nanocomposites was confirmed by ICP-MS. RESULTS: Intriguingly, molecular docking of metal oxides in the active site of nsP3 validated the binding of nanocomposites to chikungunya virus replication protein nsP3. In-vitro antiviral potential of nanocomposites were tested by performing plaque reduction assay, cytopathic effect (CPE) analysis and qRT-PCR. The nanocomposites showed significant reduction in virus titre. Half-maximal inhibitory concentration (IC50) for A/N/Z-3 and AN-5% were determined to be 2.828 and 3.277 g/mL, respectively. CPE observation and qRT-PCR results were consistent with the data obtained from plaque reduction assay for A/N/Z-3 and AN-5%. CONCLUSION: These results, have opened new avenues for development of nanocomposites based antiviral therapies.

Objective: This study aims to investigate the antiviral properties of Cow-urine distillate (CUD) and identify potential compounds responsible for its antiviral activity, thereby exploring its therapeutic potential against Chikungunya virus (CHIKV). Methods: The study assessed the antiviral activity of crude CUD using in vitro cell-based assays performed in Vero cells. The characterization of CUD was performed using GC-MS to identify potential metabolites with antiviral properties. Computational docking studies elucidated these natural compounds' binding affinities and critical interactions with CHIKV nsP2 protease (nsP2Pro). The identified metabolites were evaluated for antiviral activity against CHIKV nsP2Pro via in silico, biochemical, and cell culture-based antiviral assays. The study further investigated the synergistic antiviral effect of CUD with natural compounds such as thymoquinone (TQ) and piperine (PIP) against CHIKV replication. Results: Treatment of CHIKV with CUD resulted in 90% reduction in plaques with 2% v/v of CUD (EC50 ~ 0.423%). Furthermore, four of the compounds identified from GC-MS demonstrated substantial inhibition at non-toxic doses, as validated by FRET assay and CHIKV plaque-reduction assay. The combination of 20 µM TQ + 20 µM PIP + 2% v/v GA was found to be very effective against CHIKV, which exhibited ~4 log or 99.99% virus reduction. Conclusion: The present findings establish the antiviral potential of CUD and provide an effective natural remedy against CHIKV infection.