Non-toxic dimeric peptides derived from the bothropstoxin-I are potent SARS-CoV-2 and papain-like protease inhibitors

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Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade Federal de São Carlos (UFSCar)-
Autor(es): dc.creatorFreire, Marjorie C. L. C.-
Autor(es): dc.creatorNoske, Gabriela D.-
Autor(es): dc.creatorBitencourt, Natália V.-
Autor(es): dc.creatorSanches, Paulo R. S.-
Autor(es): dc.creatorSantos-Filho, Norival A.-
Autor(es): dc.creatorGawriljuk, Victor O.-
Autor(es): dc.creatorde Souza, Eduardo P.-
Autor(es): dc.creatorNogueira, Victor H. R.-
Autor(es): dc.creatorde Godoy, Mariana O.-
Autor(es): dc.creatorNakamura, Aline M.-
Autor(es): dc.creatorFernandes, Rafaela S.-
Autor(es): dc.creatorGodoy, Andre S.-
Autor(es): dc.creatorJuliano, Maria A.-
Autor(es): dc.creatorPeres, Bianca M.-
Autor(es): dc.creatorBarbosa, Cecília G.-
Autor(es): dc.creatorMoraes, Carolina B.-
Autor(es): dc.creatorFreitas-Junior, Lucio H. G.-
Autor(es): dc.creatorCilli, Eduardo M.-
Autor(es): dc.creatorGuido, Rafael V. C.-
Autor(es): dc.creatorOliva, Glaucius-
Data de aceite: dc.date.accessioned2025-08-21T17:15:30Z-
Data de disponibilização: dc.date.available2025-08-21T17:15:30Z-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2021-08-02-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/molecules26164896-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/229351-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/229351-
Descrição: dc.descriptionThe COVID-19 outbreak has rapidly spread on a global scale, affecting the economy and public health systems throughout the world. In recent years, peptide-based therapeutics have been widely studied and developed to treat infectious diseases, including viral infections. Herein, the antiviral effects of the lysine linked dimer des-Cys11, Lys12,Lys13-(pBthTX-I)2K ((pBthTX-I)2K)) and derivatives against SARS-CoV-2 are reported. The lead peptide (pBthTX-I)2K and derivatives showed attractive inhibitory activities against SARS-CoV-2 (EC50 = 28–65 µM) and mostly low cytotoxic effect (CC50 > 100 µM). To shed light on the mechanism of action underlying the peptides’ antiviral activity, the Main Protease (Mpro) and Papain-Like protease (PLpro) inhibitory activities of the peptides were assessed. The synthetic peptides showed PLpro inhibition potencies (IC50s = 1.0–3.5 µM) and binding affinities (Kd = 0.9–7 µM) at the low micromolar range but poor inhibitory activity against Mpro (IC50 > 10 µM). The modeled binding mode of a representative peptide of the series indicated that the compound blocked the entry of the PLpro substrate toward the protease catalytic cleft. Our findings indicated that non-toxic dimeric peptides derived from the Bothropstoxin-I have attractive cellular and enzymatic inhibitory activities, thereby suggesting that they are promising prototypes for the discovery and development of new drugs against SARS-CoV-2 infection.-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionSão Carlos Institute of Physics University of Sao Paulo, Avenida João Dagnone, 1100-
Descrição: dc.descriptionDepartment of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP)-
Descrição: dc.descriptionDepartment of Genetics and Evolution Federal University of São Carlos, Rodovia Washington Luís km 235-
Descrição: dc.descriptionThe Sao Paulo School of Medicine Federal University of São Paulo, Rua Três de Maio, 100-
Descrição: dc.descriptionDepartment of Microbiology Institute of Biomedical Sciences University of Sao Paulo, Av. Prof. Lineu Prestes, 1374-
Descrição: dc.descriptionDepartment of Pharmaceutical Sciences Federal University of São Paulo, Rua São Nicolau, 210-
Descrição: dc.descriptionDepartment of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP)-
Descrição: dc.descriptionCAPES: 001-
Descrição: dc.descriptionFAPESP: 2013/07600-3-
Descrição: dc.descriptionFAPESP: 2018/13588-0-
Descrição: dc.descriptionFAPESP: 2020/04602-9-
Descrição: dc.descriptionFAPESP: 2020/05761-3-
Descrição: dc.descriptionFAPESP: 2020/12519-4-
Descrição: dc.descriptionCNPq: 301975/2018-3-
Idioma: dc.languageen-
Relação: dc.relationMolecules-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectCOVID-19-
Palavras-chave: dc.subjectInhibitors-
Palavras-chave: dc.subjectPapain-like protease-
Palavras-chave: dc.subjectPeptides-
Palavras-chave: dc.subjectSARS-CoV-2-
Título: dc.titleNon-toxic dimeric peptides derived from the bothropstoxin-I are potent SARS-CoV-2 and papain-like protease inhibitors-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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