Evidence map›Paper›PMID 39039677›Full record

ArticleProtein and peptide letters2024

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

Paulo Ricardo da Silva Sanches, João Caldana Elias de Campos Faria, Cíntia Bittar, Hugo Alexandre Siqueira Guberovich Olivieri, Nathalya Cristina de Moraes Roso Mesquita, Gabriela Dias Noske, Andre Schutzer de Godoy, Glaucius Oliva, Paula Rahal, Eduardo Maffud Cilli

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Article in Protein and peptide letters, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Paulo Ricardo da Silva SanchesDepartment of Biological Science, School of Pharmacy, São Paulo State University (UNESP), Araraquara, SP, Brazil.
João Caldana Elias de Campos FariaDepartment of Biological Science, School of Pharmacy, São Paulo State University (UNESP), Araraquara, SP, Brazil.
Cíntia BittarDepartment of Biological Science, Institute of Bioscience, Letters and Exact Science, São Paulo State University (UNESP), Araraquara, SP, Brazil.
Hugo Alexandre Siqueira Guberovich OlivieriDepartment of Biological Science, School of Pharmacy, São Paulo State University (UNESP), Araraquara, SP, Brazil.
Nathalya Cristina de Moraes Roso MesquitaSão Carlos Institute of Physics, University of São Paulo (USP), São Carlos, SP, Brazil.
Gabriela Dias NoskeSão Carlos Institute of Physics, University of São Paulo (USP), São Carlos, SP, Brazil.
Andre Schutzer de GodoySão Carlos Institute of Physics, University of São Paulo (USP), São Carlos, SP, Brazil.
Glaucius OlivaSão Carlos Institute of Physics, University of São Paulo (USP), São Carlos, SP, Brazil.
Paula RahalDepartment of Biological Science, Institute of Bioscience, Letters and Exact Science, São Paulo State University (UNESP), Araraquara, SP, Brazil.
Eduardo Maffud CilliDepartment of Biochemistry and Organic Chemistry, Institute of Chemistry, São Paulo State University (UNESP), Araraquara, SP, Brazil.

Funding

Fundação de Amparo à Pesquisa do Estado de São Paulo 2022/11644-5,2022/05411-8,2013/07600-3,20/05761-3,20/12519-4,19/08342-4,15/23244-8National Council for Scientific Research 304739/2021-9.
6 · The paper itself

Abstract

backgroundPeptide 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.

objectiveThe 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.

methodsSolid-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.

resultsThe 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 IC

conclusionThe results highlight the antiviral potential of the GA-Hecate bioconjugate and open the door for the development of new antivirals.

Indexed as

Antiviral AgentsViral Nonstructural ProteinsVirus ReplicationZika VirusAnimalsChlorocebus aethiopsDEAD-box RNA HelicasesHumansNucleoside-TriphosphatasePeptidesProtease InhibitorsRNA HelicasesSerine EndopeptidasesVero CellsViral ProteasesZika Virus InfectionAntiviral AgentsDEAD-box RNA HelicasesNS2B protein, flavivirusNS3 protein, flavivirusNS3 protein, Zika virusNucleoside-TriphosphatasePeptidesProtease InhibitorsRNA HelicasesSerine EndopeptidasesViral Nonstructural ProteinsViral ProteasesbioconjugateflavivirusNS2B-NS3.peptidesproteaseZika virus

Identifiers

PMID39039677

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.