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Development of new peptides and bioconjugates against Zika virus infection

Grant number: 15/23244-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2016
Effective date (End): August 31, 2020
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal Investigator:Eduardo Maffud Cilli
Grantee:Paulo Ricardo da Silva Sanches
Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated research grant:13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID
Associated scholarship(s):19/08342-4 - Development of bioconjugates containing peptides for combined therapy aimed the treatment of Zika and Dengue Virus infection, BE.EP.DR

Abstract

ZIKV outbreaks highlighted the fast and silent evolution of this microrganism. Miycrocephaly and another brain disorders have been associated with ZIKV infections in newborns and adults. In 2016, Mondial Health Organization (MHO) recognized the sexual transmission of ZIKV and studies have shown that viral RNA remain in men reproductive organs during over 6 months without symptomns. Despite the efforts for the development of drugs and vaccines which could help as profilactic and treatment of infections caused by ZIKV, there is no treatment approved to this disease. The compound Gallic acid - Hecate and his N-terminal metabolites have been evaluated against Vero cells and two different lineages from ZIKV (PE243 - isolated in Brazil, 2015 and MP1751 - isolated in Uganda, 1962). Using solid phase peptide synthesis, human blood serum stability assay, viability assays using WST-1 and ELISA assay targeting envelop protein E, the results have shown that serum stability methodology is an important tool to identify new compounds based on peptide structures and proteases cleavage. GA-metabolite 5 was the most efficient synthetic compound evaluated, inhibiting both strains in all entry steps and cytoplasmic replication in three high-non-toxic concentrations (40 and 20 µM). This study has shown new synthetic antiviral targeting different steps of Zika virus replication in vitro highlighting a promising strategy to development of antiviral drugs based on peptide metabolism and bioconjugation.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BATISTA, MARIANA NOGUEIRA; DA SILVA SANCHES, PAULO RICARDO; CARNEIRO, BRUNO MOREIRA; SILVA BRAGA, ANA CLAUDIA; FERNANDES CAMPOS, GUILHERME RODRIGUES; CHILLI, EDUARDO MAFFUD; RAHAL, PAULA. GA-Hecate antiviral properties on HCV whole cycle represent a new antiviral class and open the door for the development of broad spectrum antivirals. SCIENTIFIC REPORTS, v. 8, . (17/00287-9, 16/02174-4, 13/07600-3, 15/23244-8)
SANCHES, PAULO RICARDO DA SILVA; SANCHEZ-VELAZQUEZ, RICARDO; BATISTA, MARIANA NOGUEIRA; CARNEIRO, BRUNO MOREIRA; BITTAR, CINTIA; DE LORENZO, GIUDITTA; RAHAL, PAULA; PATEL, ARVIND H.; CILLI, EDUARDO MAFFUD. Antiviral Evaluation of New Synthetic Bioconjugates Based on GA-Hecate: A New Class of Antivirals Targeting Different Steps of Zika Virus Replication. Molecules, v. 28, n. 13, p. 20-pg., . (13/07600-3, 22/05411-8, 15/23244-8, 20/05761-3, 20/12519-4, 19/08342-4)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SANCHES, Paulo Ricardo da Silva. Development of new peptides and bioconjugates against Zika Virus infection. 2020. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Instituto de Química. Araraquara Araraquara.

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Filed patent(s) as a result of this research project

COMPOSTO COM PROPRIEDADES ANTIVIRAIS CONTRA VÍRUS ZIKA BR102021014737-7 - Universidade Estadual Paulista Júlio de Mesquita Filho (Unesp) . Bruno Moreira Carneiro ; Cintia Bittar Oliva ; Eduardo Maffud Cilli ; Gabriela Miranda Ayusso ; Maria Leticia Duarte Lima ; Mariana Nogueira Batista ; Marilia de Freitas Calmon ; Paula Rahal ; Paulo Ricardo da Silva Sanches - July 2021, 27