The Potential of Metal-Organic Framework Mil-101(Al)-Nh2 in the Forefront of Antiviral Protection of Cells Via Interaction with Sars-Cov-2 Spike Rbd Protein and Their Antibacterial Action Mediated with Hypericin and Photodynamic Treatment

Abstract

The global pandemic of SARS-CoV-2 has highlighted the necessity for innovative therapeutic solutions. This research presents a new formulation utilising the metal-organic framework MIL-101(Al)-NH₂, which is loaded with hypericin, aimed at addressing viral and bacterial challenges. Hypericin, recognised for its antiviral and antibacterial efficacy, was encapsulated to mitigate its hydrophobicity, improve bioavailability, and utilise its photodynamic characteristics. The MIL-101(Al)-NH₂ Hyp complex was synthesised, characterised, and evaluated for its biological applications.Both in vitro and in vivo experiments demonstrated the effective transport of hypericin to cells that express ACE2 receptors, thereby mimicking mechanisms of viral entry. Hypericin, found in the mitochondria, demonstrated selective phototoxicity when activated by light, leading to a decrease in the metabolic activity of glioblastoma cells. The complex exhibited antibacterial efficacy, selectively targeting Gram-positive Staphylococcus epidermidis compared to Gram-negative Escherichia coli under photodynamic therapy (PDT) conditions.Fluorescence spectroscopy demonstrated the interaction between hypericin and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, which inhibits cellular uptake and colocalises with ACE2-expressing cells. The complex's dual functionality—targeting viral RBD and providing antibacterial effects via PDT—underscores its potential to mitigate complications from viral infections, such as secondary bacterial infections.The results indicate that MIL-101(Al)-NH₂ Hyp is a promising multifunctional therapeutic agent for antiviral and antibacterial applications, with potential implications for enhancing COVID-19 treatment protocols and addressing co-infections.

Keywords: MIL-101(Al)-NH2, hypericin, ACE2 receptors, RBD spike protein, Photodynamic therapy, selectivity