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.