C60-based Multivalent Glycoporphyrins Inhibit SARS-CoV-2 Specific Interaction with the DC-SIGN Transmembrane Receptor

Small. 2024 May;20(19):e2307045. doi: 10.1002/smll.202307045. Epub 2023 Dec 15.

Abstract

Since WHO has declared the COVID-19 outbreak a global pandemic, nearly seven million deaths have been reported. This efficient spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is facilitated by the ability of the spike glycoprotein to bind multiple cell membrane receptors. Although ACE2 is identified as the main receptor for SARS-CoV-2, other receptors could play a role in viral entry. Among others, C-type lectins such as DC-SIGN are identified as efficient trans-receptor for SARS-CoV-2 infection, so the use of glycomimetics to inhibit the infection through the DC-SIGN blockade is an encouraging approach. In this regard, multivalent nanostructures based on glycosylated [60]fullerenes linked to a central porphyrin scaffold have been designed and tested against DC-SIGN-mediated SARS-CoV-2 infection. First results show an outstanding inhibition of the trans-infection up to 90%. In addition, a deeper understanding of nanostructure-receptor binding is achieved through microscopy techniques, high-resolution NMR experiments, Quartz Crystal Microbalance experiments, and molecular dynamic simulations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Cell Adhesion Molecules* / antagonists & inhibitors
  • Cell Adhesion Molecules* / metabolism
  • Fullerenes* / chemistry
  • Fullerenes* / pharmacology
  • Humans
  • Lectins, C-Type* / antagonists & inhibitors
  • Lectins, C-Type* / metabolism
  • Molecular Dynamics Simulation
  • Porphyrins* / chemistry
  • Porphyrins* / pharmacology
  • Protein Binding
  • Receptors, Cell Surface* / antagonists & inhibitors
  • Receptors, Cell Surface* / metabolism
  • SARS-CoV-2* / drug effects
  • SARS-CoV-2* / metabolism
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / metabolism

Substances

  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • fullerene C60
  • Fullerenes
  • Lectins, C-Type
  • Porphyrins
  • Receptors, Cell Surface
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2