Artículo
Toward wide-spectrum antivirals against coronaviruses: Molecular characterization of SARS-CoV-2 NSP13 helicase inhibitors
Perez Lemus, Gustavo R.; Menéndez, Cintia Anabella
; Alvarado, Walter; Byléhn, Fabian; de Pablo, Juan J.
Fecha de publicación:
07/01/2022
Editorial:
Science Advances is the American Association for the Advancement of Science
Revista:
Science Advances
ISSN:
2375-2548
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
To date, effective therapeutic treatments that confer strong attenuation against coronaviruses (CoVs) remain elusive. Among potential drug targets, the helicase of CoVs is attractive due to its sequence conservation and indispensability. We rely on atomistic molecular dynamics simulations to explore the structural coordination and dynamics associated with the SARS-CoV-2 Nsp13 apo enzyme, as well as their complexes with natural ligands. A complex communication network is revealed among the five domains of Nsp13, which is differentially activated because of the presence of the ligands, as shown by shear strain analysis, principal components analysis, dynamical cross-correlation matrix analysis, and water transport analysis. The binding free energy and the corresponding mechanism of action are presented for three small molecules that were shown to be efficient inhibitors of the previous SARS-CoV Nsp13 enzyme. Together, our findings provide critical fresh insights for rational design of broad-spectrum antivirals against CoVs.
Palabras clave:
SARS-CoV-2
,
NSP13
,
antivirals
,
MD simulations
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Articulos(INQUISUR)
Articulos de INST.DE QUIMICA DEL SUR
Articulos de INST.DE QUIMICA DEL SUR
Citación
Perez Lemus, Gustavo R.; Menéndez, Cintia Anabella; Alvarado, Walter; Byléhn, Fabian; de Pablo, Juan J.; Toward wide-spectrum antivirals against coronaviruses: Molecular characterization of SARS-CoV-2 NSP13 helicase inhibitors; Science Advances is the American Association for the Advancement of Science; Science Advances; 8; 1; 7-1-2022; 1-12
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