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Volume 31, Issue 7
  • ISSN: 0929-8665
  • E-ISSN: 1875-5305

Abstract

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 IC 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.

© 2024 Bentham Science Publishers
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2024-07-01
2024-11-22

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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 Infection
PPL 31, 532 (2024); https://doi.org/10.2174/0109298665308871240703090408
/content/journals/ppl/10.2174/0109298665308871240703090408
/content/journals/ppl/10.2174/0109298665308871240703090408
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  • Article Type:     Research Article
Keyword(s): bioconjugate; flavivirus; NS2B-NS3; peptides; protease; Zika virus

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