Toward wide-spectrum antivirals against coronaviruses: Molecular characterization of SARS-CoV-2 NSP13 helicase inhibitors

dc.creatorPerez Lemus, Gustavo R.
dc.creatorMenéndez, Cintia Anabella
dc.creatorAlvarado, Walter
dc.creatorByléhn, Fabian
dc.creatorde Pablo, Juan J.
dc.date2022-01-07
dc.date.accessioned2023-08-31T00:34:16Z
dc.date.available2023-08-31T00:34:16Z
dc.identifierhttp://hdl.handle.net/11336/204359
dc.identifierPerez 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
dc.identifier2375-2548
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8543570
dc.descriptionTo 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.
dc.descriptionFil: Perez Lemus, Gustavo R.. University of Chicago; Estados Unidos
dc.descriptionFil: Menéndez, Cintia Anabella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
dc.descriptionFil: Alvarado, Walter. University of Chicago; Estados Unidos
dc.descriptionFil: Byléhn, Fabian. University of Chicago; Estados Unidos
dc.descriptionFil: de Pablo, Juan J.. University of Chicago; Estados Unidos
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherScience Advances is the American Association for the Advancement of Science
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://www.science.org/doi/10.1126/sciadv.abj4526
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/10.1126/sciadv.abj4526
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subjectSARS-CoV-2
dc.subjectNSP13
dc.subjectantivirals
dc.subjectMD simulations
dc.subjecthttps://purl.org/becyt/ford/1.4
dc.subjecthttps://purl.org/becyt/ford/1
dc.titleToward wide-spectrum antivirals against coronaviruses: Molecular characterization of SARS-CoV-2 NSP13 helicase inhibitors
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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