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

Author(s)

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

• Document type: Journal article
• Source: Molecules; v. 28, n. 13, p. 20-pg., 2023-07-01.

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. (AU)

• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 22/05411-8 - Development of peptide/guanidine bioconjugates with anti-Leishmania activity
• Grantee: Eduardo Maffud Cilli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/23244-8 - Development of new peptides and bioconjugates against Zika virus infection
• Grantee: Paulo Ricardo da Silva Sanches
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/05761-3 - Study of the action of synthetic peptides as antivirals against SARS-CoV-2 (COVID-19) and combined evaluation with commercial anti-inflammatories
• Grantee: Eduardo Maffud Cilli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/12519-4 - Study of the action of synthetic peptides as antivirals against SARS-CoV-2 (COVID-19) and combined evaluation with commercial anti-inflammatories
• Grantee: Paulo Ricardo da Silva Sanches
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/08342-4 - Development of bioconjugates containing peptides for combined therapy aimed the treatment of Zika and Dengue Virus infection
• Grantee: Paulo Ricardo da Silva Sanches
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate