Artículo
Molecular characterization of ebselen binding activity to SARS-CoV-2 main protease
Menéndez, Cintia Anabella
; Byléhn, Fabian; Perez Lemus, Gustavo R.; Alvarado, Walter; de Pablo, Juan J.
Fecha de publicación:
09/2020
Editorial:
Science Advances is the American Association for the Advancement of Science
Revista:
Science Advances
e-ISSN:
2375-2548
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
There is an urgent need to repurpose drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent computational-experimental screenings have identified several existing drugs that could serve as effective inhibitors of the virus? main protease, Mpro, which is involved in gene expression and replication. Among these, ebselen (2-phenyl-1,2-benzoselenazol-3-one) appears to be particularly promising. Here, we examine, at a molecular level, the potential of ebselen to decrease Mpro activity. We find that it exhibits a distinct affinity for the catalytic region. Our results reveal a higher-affinity, previously unknown binding site localized between the II and III domains of the protein. A detailed strain analysis indicates that, on such a site, ebselen exerts a pronounced allosteric effect that regulates catalytic site access through surface-loop interactions, thereby inducing a reconfiguration of water hotspots. Together, these findings highlight the promise of ebselen as a repurposed drug against SARS-CoV-2.
Palabras clave:
EBSELEN
,
SARS-COV-2
,
MOLECULAR DYNAMIC SIMULATION
,
COVID-19
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Colecciones
Articulos(INQUISUR)
Articulos de INST.DE QUIMICA DEL SUR
Articulos de INST.DE QUIMICA DEL SUR
Citación
Menéndez, Cintia Anabella; Byléhn, Fabian; Perez Lemus, Gustavo R.; Alvarado, Walter; de Pablo, Juan J.; Molecular characterization of ebselen binding activity to SARS-CoV-2 main protease; Science Advances is the American Association for the Advancement of Science; Science Advances; 6; 37; 9-2020
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