The GA-Hecate Peptide inhibits the ZIKV Replicative Cycle in Different Steps and can Inhibit the Flavivirus NS2B-NS3 Protease after Cell Infection

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Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.creatorSanches, Paulo Ricardo da Silva-
Autor(es): dc.creatorFaria, João Caldana Elias de Campos-
Autor(es): dc.creatorBittar, Cíntia-
Autor(es): dc.creatorOlivieri, Hugo Alexandre Siqueira Guberovich-
Autor(es): dc.creatorMesquita, Nathalya Cristina de Moraes Roso-
Autor(es): dc.creatorNoske, Gabriela Dias-
Autor(es): dc.creatorde Godoy, Andre Schutzer-
Autor(es): dc.creatorOliva, Glaucius-
Autor(es): dc.creatorRahal, Paula-
Autor(es): dc.creatorCilli, Eduardo Maffud-
Data de aceite: dc.date.accessioned2025-08-21T18:05:01Z-
Data de disponibilização: dc.date.available2025-08-21T18:05:01Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2023-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.2174/0109298665308871240703090408-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/299193-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/299193-
Descrição: dc.descriptionBackground: Peptide drugs are advantageous because they are subject to rational design and exhibit highly diverse structures and broad biological activities. The NS2B-NS3 protein is a particularly promising flavivirus therapeutic target, with extensive research on the development of inhibitors as therapeutic candidates, and was used as a model in this work to determine the mechanism by which GA-Hecate inhibits ZIKV replication. Objective: The present study aimed to evaluate the potential of GA-Hecate, a new antiviral developed by our group, against the Brazilian Zika virus and to evaluate the mechanism of action of this compound on the flavivirus NS2B-NS3 protein. Methods: Solid-phase peptide Synthesis, High-Performance Liquid Chromatography, and Mass Spectrometry were used to obtain, purify, and characterize the synthesized compound. Real-time and enzymatic assays were used to determine the antiviral potential of GA-Hecate against ZIKV. Results: The RT-qPCR results showed that GA-Hecate decreased the number of ZIKV RNA copies in the virucidal, pre-treatment, and post-entry assays, with 5-to 6-fold fewer RNA copies at the higher nontoxic concentration in Vero cells (HNTC: 10 μM) than in the control cells. Enzymatic and kinetic assays indicated that GA-Hecate acts as a competitive ZIKV NS2B-NS3 protease inhibitor with an IC50 of 32 nM and has activity against the yellow fever virus protease. Conclusion: The results highlight the antiviral potential of the GA-Hecate bioconjugate and open the door for the development of new antivirals.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionDepartment of Biological Science School of Pharmacy São Paulo State University (UNESP), SP-
Descrição: dc.descriptionDepartment of Biological Science Institute of Bioscience Letters and Exact Science São Paulo State University (UNESP), SP-
Descrição: dc.descriptionSão Carlos Institute of Physics University of São Paulo (USP), SP-
Descrição: dc.descriptionDepartment of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP), SP-
Descrição: dc.descriptionDepartment of Biological Science School of Pharmacy São Paulo State University (UNESP), SP-
Descrição: dc.descriptionDepartment of Biological Science Institute of Bioscience Letters and Exact Science São Paulo State University (UNESP), SP-
Descrição: dc.descriptionDepartment of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP), SP-
Descrição: dc.descriptionFAPESP: 15/23244-8-
Descrição: dc.descriptionFAPESP: 19/08342-4-
Descrição: dc.descriptionFAPESP: 20/05761-3-
Descrição: dc.descriptionFAPESP: 20/12519-4-
Descrição: dc.descriptionFAPESP: 2013/07600-3-
Descrição: dc.descriptionFAPESP: 2022/05411-8-
Descrição: dc.descriptionFAPESP: 2022/11644-5-
Formato: dc.format532-543-
Idioma: dc.languageen-
Relação: dc.relationProtein and Peptide Letters-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectbioconjugate-
Palavras-chave: dc.subjectflavivirus-
Palavras-chave: dc.subjectNS2B-NS3-
Palavras-chave: dc.subjectpeptides-
Palavras-chave: dc.subjectprotease-
Palavras-chave: dc.subjectZika virus-
Título: dc.titleThe GA-Hecate Peptide inhibits the ZIKV Replicative Cycle in Different Steps and can Inhibit the Flavivirus NS2B-NS3 Protease after Cell Infection-
Tipo de arquivo: dc.typelivro digital-
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