Silver nanoparticles interact with HIV-1 in a size-dependent manner, with nanoparticles between 1–10 nm attaching to the virus. The interaction is likely due to preferential binding to the gp120 glycoprotein knobs on the viral envelope. Silver nanoparticles inhibit HIV-1 from binding to host cells, as shown in vitro. The study characterized three silver nanoparticle preparations: carbon-coated, PVP-coated, and BSA-coated. TEM and UV-Vis spectroscopy revealed size and shape distributions, with carbon-coated nanoparticles showing a broad size range and PVP- and BSA-coated nanoparticles being smaller and more spherical. HAADF imaging showed regular spatial arrangements of nanoparticles on the HIV-1 virus, correlating with the positions of gp120 glycoprotein knobs. The interaction of nanoparticles with the virus is likely due to binding to exposed sulfur-bearing residues on the gp120 knobs. Silver nanoparticles inhibit HIV-1 infectivity in vitro, with higher inhibitory effects observed for nanoparticles released from the carbon matrix. The toxicity of the nanoparticles varied depending on their surface chemistry, with carbon-coated nanoparticles showing higher cytotoxicity. The study highlights the potential of silver nanoparticles as antimicrobial agents and underscores the importance of understanding nanoparticle interactions with viruses and microorganisms. Future research should explore the long-term effects of nanoparticles and their impact on complex biosystems.Silver nanoparticles interact with HIV-1 in a size-dependent manner, with nanoparticles between 1–10 nm attaching to the virus. The interaction is likely due to preferential binding to the gp120 glycoprotein knobs on the viral envelope. Silver nanoparticles inhibit HIV-1 from binding to host cells, as shown in vitro. The study characterized three silver nanoparticle preparations: carbon-coated, PVP-coated, and BSA-coated. TEM and UV-Vis spectroscopy revealed size and shape distributions, with carbon-coated nanoparticles showing a broad size range and PVP- and BSA-coated nanoparticles being smaller and more spherical. HAADF imaging showed regular spatial arrangements of nanoparticles on the HIV-1 virus, correlating with the positions of gp120 glycoprotein knobs. The interaction of nanoparticles with the virus is likely due to binding to exposed sulfur-bearing residues on the gp120 knobs. Silver nanoparticles inhibit HIV-1 infectivity in vitro, with higher inhibitory effects observed for nanoparticles released from the carbon matrix. The toxicity of the nanoparticles varied depending on their surface chemistry, with carbon-coated nanoparticles showing higher cytotoxicity. The study highlights the potential of silver nanoparticles as antimicrobial agents and underscores the importance of understanding nanoparticle interactions with viruses and microorganisms. Future research should explore the long-term effects of nanoparticles and their impact on complex biosystems.