The GA-Hecate Peptide inhibits the ZIKV Replicative Cycle in Different Steps and can Inhibit the Flavivirus NS2B-NS3 Protease after Cell Infection
Background: 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 th...
| Autores: | , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | Brasil |
| Recursos: | Universidade Estadual Paulista (UNESP) |
| Repositorio: | Repositório Institucional da UNESP |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.unesp.br:11449/299193 |
| Acesso em linha: | http://dx.doi.org/10.2174/0109298665308871240703090408 https://hdl.handle.net/11449/299193 |
| Access Level: | acceso abierto |
| Palavra-chave: | bioconjugate flavivirus NS2B-NS3 peptides protease Zika virus |
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The GA-Hecate Peptide inhibits the ZIKV Replicative Cycle in Different Steps and can Inhibit the Flavivirus NS2B-NS3 Protease after Cell InfectionbioconjugateflavivirusNS2B-NS3peptidesproteaseZika virusBackground: 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Biological Science School of Pharmacy São Paulo State University (UNESP), SPDepartment of Biological Science Institute of Bioscience Letters and Exact Science São Paulo State University (UNESP), SPSão Carlos Institute of Physics University of São Paulo (USP), SPDepartment of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP), SPDepartment of Biological Science School of Pharmacy São Paulo State University (UNESP), SPDepartment of Biological Science Institute of Bioscience Letters and Exact Science São Paulo State University (UNESP), SPDepartment of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP), SPFAPESP: 15/23244-8FAPESP: 19/08342-4FAPESP: 20/05761-3FAPESP: 20/12519-4FAPESP: 2013/07600-3FAPESP: 2022/05411-8FAPESP: 2022/11644-5Universidade Estadual Paulista (UNESP)Universidade de São Paulo (USP)2025-04-29T18:41:38Z2024-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article532-543http://dx.doi.org/10.2174/0109298665308871240703090408Protein and Peptide Letters, v. 31, n. 7, p. 532-543, 2024.1875-53050929-8665https://hdl.handle.net/11449/29919310.2174/01092986653088712407030904082-s2.0-85203356662Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengProtein and Peptide Lettersinfo:eu-repo/semantics/openAccessSanches, Paulo Ricardo da Silva [UNESP]Faria, João Caldana Elias de Campos [UNESP]Bittar, Cíntia [UNESP]Olivieri, Hugo Alexandre Siqueira Guberovich [UNESP]Mesquita, Nathalya Cristina de Moraes RosoNoske, Gabriela Diasde Godoy, Andre SchutzerOliva, GlauciusRahal, Paula [UNESP]Cilli, Eduardo Maffud [UNESP]2025-05-28T05:38:46Zoai:repositorio.unesp.br:11449/299193Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462025-05-28T05:38:46Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
| dc.title.none.fl_str_mv |
The GA-Hecate Peptide inhibits the ZIKV Replicative Cycle in Different Steps and can Inhibit the Flavivirus NS2B-NS3 Protease after Cell Infection |
| title |
The GA-Hecate Peptide inhibits the ZIKV Replicative Cycle in Different Steps and can Inhibit the Flavivirus NS2B-NS3 Protease after Cell Infection |
| spellingShingle |
The GA-Hecate Peptide inhibits the ZIKV Replicative Cycle in Different Steps and can Inhibit the Flavivirus NS2B-NS3 Protease after Cell Infection Sanches, Paulo Ricardo da Silva [UNESP] bioconjugate flavivirus NS2B-NS3 peptides protease Zika virus |
| title_short |
The GA-Hecate Peptide inhibits the ZIKV Replicative Cycle in Different Steps and can Inhibit the Flavivirus NS2B-NS3 Protease after Cell Infection |
| title_full |
The GA-Hecate Peptide inhibits the ZIKV Replicative Cycle in Different Steps and can Inhibit the Flavivirus NS2B-NS3 Protease after Cell Infection |
| title_fullStr |
The GA-Hecate Peptide inhibits the ZIKV Replicative Cycle in Different Steps and can Inhibit the Flavivirus NS2B-NS3 Protease after Cell Infection |
| title_full_unstemmed |
The GA-Hecate Peptide inhibits the ZIKV Replicative Cycle in Different Steps and can Inhibit the Flavivirus NS2B-NS3 Protease after Cell Infection |
| title_sort |
The GA-Hecate Peptide inhibits the ZIKV Replicative Cycle in Different Steps and can Inhibit the Flavivirus NS2B-NS3 Protease after Cell Infection |
| dc.creator.none.fl_str_mv |
Sanches, Paulo Ricardo da Silva [UNESP] Faria, João Caldana Elias de Campos [UNESP] Bittar, Cíntia [UNESP] Olivieri, Hugo Alexandre Siqueira Guberovich [UNESP] Mesquita, Nathalya Cristina de Moraes Roso Noske, Gabriela Dias de Godoy, Andre Schutzer Oliva, Glaucius Rahal, Paula [UNESP] Cilli, Eduardo Maffud [UNESP] |
| author |
Sanches, Paulo Ricardo da Silva [UNESP] |
| author_facet |
Sanches, Paulo Ricardo da Silva [UNESP] Faria, João Caldana Elias de Campos [UNESP] Bittar, Cíntia [UNESP] Olivieri, Hugo Alexandre Siqueira Guberovich [UNESP] Mesquita, Nathalya Cristina de Moraes Roso Noske, Gabriela Dias de Godoy, Andre Schutzer Oliva, Glaucius Rahal, Paula [UNESP] Cilli, Eduardo Maffud [UNESP] |
| author_role |
author |
| author2 |
Faria, João Caldana Elias de Campos [UNESP] Bittar, Cíntia [UNESP] Olivieri, Hugo Alexandre Siqueira Guberovich [UNESP] Mesquita, Nathalya Cristina de Moraes Roso Noske, Gabriela Dias de Godoy, Andre Schutzer Oliva, Glaucius Rahal, Paula [UNESP] Cilli, Eduardo Maffud [UNESP] |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) Universidade de São Paulo (USP) |
| dc.subject.por.fl_str_mv |
bioconjugate flavivirus NS2B-NS3 peptides protease Zika virus |
| topic |
bioconjugate flavivirus NS2B-NS3 peptides protease Zika virus |
| description |
Background: 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. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024-01-01 2025-04-29T18:41:38Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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http://dx.doi.org/10.2174/0109298665308871240703090408 Protein and Peptide Letters, v. 31, n. 7, p. 532-543, 2024. 1875-5305 0929-8665 https://hdl.handle.net/11449/299193 10.2174/0109298665308871240703090408 2-s2.0-85203356662 |
| url |
http://dx.doi.org/10.2174/0109298665308871240703090408 https://hdl.handle.net/11449/299193 |
| identifier_str_mv |
Protein and Peptide Letters, v. 31, n. 7, p. 532-543, 2024. 1875-5305 0929-8665 10.2174/0109298665308871240703090408 2-s2.0-85203356662 |
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eng |
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eng |
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Protein and Peptide Letters |
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openAccess |
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532-543 |
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