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Org Lett ; 26(27): 5700-5704, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38935522

RESUMEN

Protein adenosine diphosphate (ADP)-ribosylation is crucial for a proper immune response. Accordingly, viruses have evolved ADP-ribosyl hydrolases to remove these modifications, a prominent example being the SARS-CoV-2 NSP3 macrodomain, "Mac1". Consequently, inhibitors are developed by testing large libraries of small molecule candidates, with considerable success. However, a relatively underexplored angle in design pertains to the synthesis of structural substrate mimics. Here, we present the synthesis and biophysical activity of novel adenosine diphosphate ribose (ADPr) analogues as SARS-CoV-2 NSP3 Mac1 inhibitors.


Asunto(s)
Adenosina Difosfato Ribosa , Antivirales , SARS-CoV-2 , SARS-CoV-2/efectos de los fármacos , Adenosina Difosfato Ribosa/química , Adenosina Difosfato Ribosa/metabolismo , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Humanos , Estructura Molecular , Tratamiento Farmacológico de COVID-19 , Dominios Proteicos
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