Antiviral evaluation of new synthetic bioconjugates based on GA-Hecate: A new class of antivirals targeting different steps of Zika Virus replication

da Silva Sanches, P. R., Sanchez-Velazquez, R., Nogueira Batista, M., Moreira Carneiro, B., Bittar, C., De Lorenzo, G. , Rahal, P., Patel, A. H. and Maffud Cilli, E. (2023) Antiviral evaluation of new synthetic bioconjugates based on GA-Hecate: A new class of antivirals targeting different steps of Zika Virus replication. Molecules, 28(13), 4884. (doi: 10.3390/molecules28134884) (PMID:37446546) (PMCID:PMC10343505)

Abstract

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-CONH2)—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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: De Lorenzo, Dr Giuditta and Patel, Professor Arvind
• Authors: da Silva Sanches, P. R., Sanchez-Velazquez, R., Nogueira Batista, M., Moreira Carneiro, B., Bittar, C., De Lorenzo, G., Rahal, P., Patel, A. H., and Maffud Cilli, E.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Molecules
• Publisher: MDPI
• ISSN: 1420-3049
• ISSN (Online): 1420-3049
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Molecules 28(13):4884
• Publisher Policy: Reproduced under a Creative Commons licence

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172630		Basis of the host range and tissue tropism for hepatitis C virus	Arvind Patel	Medical Research Council (MRC)	MC_UU_12014/2	III - Centre for Virus Research