The aminoadamantane derivative 3F2 modulates monocyte and NK cell activation and restores immune mediators altered by Monkeypox virus stimuli.

The monkeypox virus (MPV) is known to employ multiple immune evasion strategies that compromise antiviral defenses and disrupt immune homeostasis. Here, we characterized the immune responses induced by stimulation with inactivated MPV and evaluated the ability of aminoadamantane (AMA) and its derivative, 3F2, to restore immune function. Peripheral blood mononuclear cells that were stimulated with MPV exhibited altered activation in a subset of monocytes, along with suppressed activation of natural killer (NK) and natural killer T (NKT) cells. MPV stimulation also led to significant changes in the levels of immunosoluble mediators, including reductions in chemokines and cytokines that are crucial for antiviral defense and immune regulation. Treatment with 3F2 proved to be more effective than AMA, resulting in significantly higher levels of CCL2, CXCL8, IFN-γ, IL-12(p40), IL-15, IL-5, and essential growth factors such as VEGF and NGF-β. Furthermore, 3F2 treatment partially reverses monocyte activation and re-establishes NK and NKT cell function. The current results indicate that 3F2 can control inflammation while preserving antiviral responsiveness. These findings demonstrate that inactivated MPV stimuli profoundly modulates innate immune activation and identify 3F2 as a promising immunomodulatory candidate capable of partially restoring immune responses altered by viral particle stimulation.