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Small ; 20(19): e2307045, 2024 May.
Article in English | MEDLINE | ID: mdl-38100142

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.


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