In Silico Evaluation of Interactions Between Graphene Oxide With Heparin and HSV-1 Glycoproteins as a Potential Antiviral Strategy

The herpes simplex virus type 1 (HSV-1) is a highly prevalent pathogen responsible for recurrent infections, whose conventional therapy based on nucleoside analogs faces limitations, including the emergence of resistant strains. In this context, nanomaterials have stood out as innovative strategies in the development of antiviral agents, either as direct inhibitors or as controlled drug-delivery systems. In this study, we investigated the potential of graphene oxide (GO) functionalized with heparin (GO@Heparina) to interact with HSV-1 glycoproteins through molecular docking simulations. Cytotoxicity studies have already been carried out in VERO cells with different formulations (GO, GO@Heparina 2.5% and 5.0%, and heparin alone), with results supporting cell viability at specific concentrations, indicating a satisfactory safety profile. Based on these data, we conducted in silico analyses using the crystallographic structures of glycoproteins gB (PDB ID: 2GUM) and gH-gL (PDB ID: 3M1C), involved in viral fusion and entry processes. The results indicated that GO@Heparina shows affinities higher than those of heparin alone in all tested domains of gB (domains I to V), with binding energies ranging from -10.2 to -11.6 kilocalories per mol (kcal/mol) and a minimum inhibition constant (Ki) of 3.14 micromolar (µM) in domain I. In contrast, heparin alone exhibited affinities between -6.9 and -8.7 kcal/mol, with emphasis on the lower efficiency in domain II of gB. In the gH-gL complex, GO@Heparina also demonstrated superior performance (binding free energy ΔG = -9.0 kcal/mol; Ki = 252.91 µM), compared with heparin alone (ΔG = -6.0 kcal/mol; Ki = 39.99 µM), corroborating its greater interaction stability. Functionalization of GO seems to optimize the orientation and distribution of heparin’s electrostatic and hydrophobic interactions with critical residues of these viral proteins, suggesting a potential mechanism for blocking viral entry. We conclude that GO@Heparina represents a promising nanobiotechnological system for antiviral applications against HSV-1. The next stage of the project consists of experimental in vitro validation of the antiviral activity of these formulations against HSV-1, in order to confirm their therapeutic efficacy.