GA-Hecate antiviral properties on HCV whole cycle represent a new antiviral class and open the door for the development of broad spectrum antivirals

Author(s)

Batista, Mariana Nogueira ^[1] ; da Silva Sanches, Paulo Ricardo ^[2] ; Carneiro, Bruno Moreira ^[1] ; Silva Braga, Ana Claudia ^[1] ; Fernandes Campos, Guilherme Rodrigues ^[1] ; Chilli, Eduardo Maffud ^[2] ; Rahal, Paula ^[1]

Affiliation

^[1] UNESP Sao Paulo State Univ, Inst Biosci Language & Exact Sci, Sao Jose Do Rio Preto, SP - Brazil

^[2] UNESP Sao Paulo State Univ, Inst Chem, Araraquara, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 8, SEP 25 2018.
• Web of Science Citations: 0

Abstract

In recent years, synthetic peptides have been considered promising targets for drug development that possess low side-effects, are cost-effective and are susceptible to rational design. Hecate was initially described as a potent bacterial inhibitor and subsequently as an anticancer drug with functions related to its lipid interaction property. Viruses, such as hepatitis C virus (HCV), have a lipid-dependent life cycle and could be affected by Hecate in many ways. Here, we assessed modifications on Hecate's N-terminus region and its effects on HCV and hepatotoxicity. Gallic acid-conjugated Hecate was the most efficient Hecate-derivative, presenting high potential as an antiviral and inhibiting between 50 to 99% of all major steps within the HCV infectious cycle. However, the most promising aspect was GA-Hecate's mechanism of action, which was associated with a balanced lipid interaction with the viral envelope and lipid droplets, as well as dsRNA intercalation, allowing for the possibility to affect other ssRNA viruses and those with a lipid-dependent cycle. (AU)

• FAPESP's process: 17/00287-9 - Adaptation of a rat derived HCV-RELATED rodent HEPACIVIRUS to the mouse host
• Grantee: Mariana Nogueira Batista
• Support type: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 16/02174-4 - Assessment of synthetic peptides on directed Hepatitis C Virus inhibition
• Grantee: Mariana Nogueira Batista
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/23244-8 - Development of multifunctional prodrugs for combination therapy against hepatocellular carcinoma and HCV
• Grantee: Paulo Ricardo da Silva Sanches
• Support type: Scholarships in Brazil - Doctorate