Cellular uptake of metal oxide-based nanocomposites and targeting of chikungunya virus replication protein nsP3

Emergence of new pathogenic viruses along with adaptive potential of RNA viruses has become a major public health concern. Therefore, it is increasingly crucial to investigate and assess the antiviral potential of nanocomposites, which is constantly advancing area of medical biology. In this study, two types of nanocomposites: Ag/NiO and Ag₂O/NiO/ZnO with varying molar ratios of silver and silver oxide, respectively have been synthesised and characterised. Three metal/metal oxide (Ag/NiO) composites having different amounts of Ag nanoparticles (NPs) anchored on NiO octahedrons are AN-5 % (5 % Ag), AN-10 % (10 % Ag) and AN-15 % (15 % Ag)) and three ternary metal oxide nanocomposites (Ag₂O/NiO/ZnO) i.e., A/N/Z-1, A/N/Z-2, and A/N/Z-3 with different molar ratios of silver oxide (10 %, 20 % and 30 %, respectively) were evaluated for their antiviral potential. Cellular uptake of nanocomposites was confirmed by ICP-MS. 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 was 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 µg/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 %. These results have opened new avenues for development of nanocomposites based antiviral therapies.