Gold nanoparticles as dual-action antiviral agents: disruption of SARS-CoV-2 viral envelopes and RNA integrity.

Gold nanoparticles (AuNPs) possess unique physicochemical properties that enable interactions with viral particles; however, most reported antiviral studies rely on surface-functionalized nanoparticles or indirect assays without direct structural evaluation of viral components. In this study, we investigated the in vitro interaction of citrate-capped (non-functionalized) AuNPs with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical samples using a combined approach integrating molecular detection, sequencing, and atomic force microscopy (AFM). Cytotoxicity assays in HEK293T and A549 human cell lines demonstrated that AuNPs were well tolerated at lower concentrations (0.1 and 0.5 nM) over 24 and 72 h. However, exposure to 1 nM for 72 h reduced viability to ~ 60%, indicating dose- and time-dependent effects without definitive cytotoxicity. AuNP exposure was associated with reduced RT-qPCR-detectable viral RNA in four clinical samples, with variable responses (complete reduction in 2/4 samples and partial reduction in 2/4 samples). These findings reflect changes in RNA detectability rather than confirmed inhibition of viral infectivity. AFM analysis demonstrated time-dependent structural perturbation of model single-stranded RNA under simplified in vitro conditions, while whole-genome sequencing did not show evidence of viral genome fragmentation. Collectively, these findings provide a mechanistic indication that non-functionalized AuNPs may contribute to viral particle destabilization rather than direct genomic degradation. This study highlights a combined biophysical and molecular framework to evaluate nanoparticle-virus interactions using patient-derived samples. Further studies incorporating infectivity assays and in vivo models are required to determine therapeutic relevance.