Antiviral Evaluation of New Synthetic Bioconjugates Based on GA-Hecate: A New Class of Antivirals Targeting Different Steps of Zika Virus Replication.

Autor: da Silva Sanches PR; School of Pharmaceutical Science, São Paulo State University, Araraquara 14800-903, SP, Brazil.; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G12 8QQ, UK.; Institute of Chemistry, São Paulo State University, Araraquara 14800-900, SP, Brazil., Velazquez RS; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G12 8QQ, UK., Batista MN; Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, NY 10065, USA., Carneiro BM; School of Health Science, Federal University of Rondonópolis, Rondonópolis 78736-900, MT, Brazil., Bittar C; School of Health Science, Federal University of Rondonópolis, Rondonópolis 78736-900, MT, Brazil., De Lorenzo G; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G12 8QQ, UK., Rahal P; Institute of Bioscience, Humanities and Exact Science, São Paulo State University, São José do Rio Preto 15054-000, SP, Brazil., Patel AH; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G12 8QQ, UK., Cilli EM; Institute of Chemistry, São Paulo State University, Araraquara 14800-900, SP, Brazil.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2023 Jun 21; Vol. 28 (13). Date of Electronic Publication: 2023 Jun 21.
DOI: 10.3390/molecules28134884
Abstrakt: Re-emerging arboviruses represent a serious health problem due to their rapid vector-mediated spread, mainly in urban tropical areas. The 2013-2015 Zika virus (ZIKV) outbreak in South and Central America has been associated with cases of microcephaly in newborns and Guillain-Barret syndrome. We previously showed that the conjugate gallic acid-Hecate (GA-FALALKALKKALKKLKKALKKAL-CONH 2 )-is an efficient inhibitor of the hepatitis C virus. Here, we show that the Hecate peptide is degraded in human blood serum into three major metabolites. These metabolites conjugated with gallic acid were synthesized and their effect on ZIKV replication in cultured cells was evaluated. The GA-metabolite 5 (GA-FALALKALKKALKKL-COOH) was the most efficient in inhibiting two ZIKV strains of African and Asian lineage at the stage of both virus entry (virucidal and protective) and replication (post-entry). We also demonstrate that GA-metabolite 5 does not affect cell growth after 7 days of continuous treatment. Thus, this study identifies a new synthetic antiviral compound targeting different steps of ZIKV replication in vitro and with the potential for broad reactivity against other flaviviruses. Our work highlights a promising strategy for the development of new antivirals based on peptide metabolism and bioconjugation.
Databáze: MEDLINE
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