Molecularly Imprinted Polymer Nanoparticles for Reducing Herpes Simplex Virus Type 2 Infection

Molecularly imprinted polymer nanoparticles (nanoMIPs) were synthesized via solid-phase imprinting for the selective recognition and inhibition of herpes simplex virus type 2 (HSV-2). An optimized copolymer composition yielded spherical nanoMIPs with a hydrodynamic diameter of 146 ± 4 nm, comparable to that of HSV-2 virions (94 ± 6 nm). Electrochemical analysis showed a 3-fold higher current shift for HSV-2-imprinted nanoMIPs compared to nonimprinted controls, confirming enhanced binding ability toward HSV-2. The nanoMIPs exhibited highly preferential recognition of HSV-2 over related viruses, with cross-reactivity of 62 ± 2% for HSV-1, 30 ± 1% for human papillomavirus type 16, and less than 3% for hepatitis B virus and dengue virus type 1. The cytotoxicity assay confirmed that the nanoMIPs were biocompatible with Vero cells and human primary peripheral blood mononuclear cells at concentrations up to 2.92 × 10⁶ particles/mL. The nanoMIPs significantly reduced HSV-2 infection during the early stages of infection, achieving inhibition efficiencies of 80 ± 1% and 49 ± 3% in virus pretreatment and cotreatment groups, respectively. This antiviral mechanism is attributed to direct binding of nanoMIPs to intact viral particles and masking of viral glycoproteins required for host cell attachment, leading to blocking the infection pathway. The nanoMIPs maintained robust antiviral efficacy under extreme conditions, retaining inhibition efficiencies of 73 ± 6% at pH 4.0, 67 ± 5% at pH 10.0, and 63 ± 2% following autoclave sterilization. These findings demonstrate that nanoMIPs function as highly stable, robust, and selective biomimetic receptors, offering a promising platform for antiviral nanomedicine and the prevention of HSV-2 transmission.