The potential of metal-organic framework MIL-101(Al)-NHin 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.

in Journal of colloid and interface science by Veronika Huntošová, Anass Benziane, Luboš Zauška, Luboš Ambro, Soňa Olejárová, Jaroslava Joniová, Nina Hlávková, Georges Wagnières, Gabriela Zelenková, Pavel Diko, Jozef Bednarčík, Florina Zákány, Tamás Kovács, Erik Sedlák, György Vámosi, Miroslav Almáši

TLDR

  • The study presents a novel therapeutic solution, MIL-101(Al)-NHHyp, for addressing viral and bacterial challenges, demonstrating its potential to mitigate complications of SARS-CoV-2 infections.

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)-NH, 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)-NHHyp complex was synthesised, characterised, and evaluated for its biological applications for the first time. The main objective of this study was to demonstrate the multimodal potential of such a construct, in particular the effect on SARS-CoV-2 protein levels and its interaction with cells. 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. In addition, hypericin found in the mitochondria showed selective phototoxicity when activated by light, leading to a decrease in the metabolic activity of glioblastoma cells. Importantly, the complex also showed antibacterial efficacy by selectively targeting Gram-positive Staphylococcus epidermidis compared to Gram-negative Escherichia coli under photodynamic therapy (PDT) conditions. To our knowledge, this study was the first to demonstrate the interaction between hypericin, MIL-101(Al)-NHand the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, which inhibits cellular uptake and colocalises with ACE2-expressing cells. Therefore, the dual functionality of the complex - targeting the viral RBD and the antibacterial effect via PDT - emphasises its potential to mitigate complications of viral infections, such as secondary bacterial infections. In summary, these results suggest that MIL-101(Al)-NHHyp is a promising multifunctional therapeutic agent for antiviral and antibacterial applications, potentially contributing to the improvement of COVID-19 treatment protocols and the treatment of co-infections.

Overview

  • The study develops a new therapeutic solution utilising metal-organic framework MIL-101(Al)-NH loaded with hypericin to address viral and bacterial challenges, aiming to mitigate complications of SARS-CoV-2 infections.
  • The main objective is to demonstrate the multimodal potential of the MIL-101(Al)-NHHyp complex in inhibiting cellular uptake of SARS-CoV-2 and exhibiting antibacterial efficacy.
  • The study involved synthesising, characterising, and evaluating the biological applications of the MIL-101(Al)-NHHyp complex, including in vitro and in vivo experiments to investigate its effects on SARS-CoV-2 protein levels, cell interaction, and cellular metabolism.

Comparative Analysis & Findings

  • In vitro experiments demonstrated the effective transport of hypericin to cells that express ACE2 receptors, mimicking viral entry mechanisms.
  • In vivo experiments showed the complex's ability to selectively target Gram-positive Staphylococcus epidermidis bacteria under photodynamic therapy (PDT) conditions, whereas it had no effect on Gram-negative Escherichia coli.
  • The study found the interaction between hypericin, MIL-101(Al)-NH, and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, inhibiting cellular uptake and colocalising with ACE2-expressing cells.

Implications and Future Directions

  • The dual functionality of MIL-101(Al)-NHHyp, targeted towards the viral RBD and antibacterial effect via PDT, suggests its potential to mitigate complications of viral infections, such as secondary bacterial infections.
  • Future studies could focus on evaluating the complex's efficacy in animal models and clinical trials to confirm its therapeutic potential.
  • Developing and enhancing the multimodal properties of MIL-101(Al)-NHHyp could lead to improved treatment protocols for COVID-19 and co-infections.
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