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

Abstract

AbstractSince 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.