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Small ; 20(19): e2307045, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38100142

RESUMO

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.


Assuntos
Moléculas de Adesão Celular , Fulerenos , Lectinas Tipo C , Porfirinas , Receptores de Superfície Celular , SARS-CoV-2 , Humanos , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/antagonistas & inibidores , COVID-19/virologia , Tratamento Farmacológico da COVID-19 , Fulerenos/química , Fulerenos/farmacologia , Lectinas Tipo C/metabolismo , Lectinas Tipo C/antagonistas & inibidores , Simulação de Dinâmica Molecular , Porfirinas/química , Porfirinas/farmacologia , Ligação Proteica , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/antagonistas & inibidores , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química
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