Natural phenolic compounds scaffolds in design of dengue virus inhibitors

• Grant number: 23/10328-5
• Support Opportunities: Scholarships in Brazil - Support Program for Fixating Young Doctors
• Start date: August 01, 2023
• End date: June 30, 2025
• Field of knowledge: Health Sciences - Pharmacy - Pharmacognosy
• Agreement: CNPq
• Principal Investigator: Ian Castro-Gamboa
• Grantee: Luiz Antonio Dutra
• Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 23/01633-9 - Natural phenolic compounds scaffolds in design of Dengue virus inhibitors, AP.R

Abstract

Dengue is a febrile infectious disease caused by the DENV virus, and has become a worldwide health crisis. The transmission of DENV virus by the Aedes aegypit vector in Brazil causes profound impacts on the health system, where vaccines and drugs for these diseases are non-existent. Exploring key mechanisms or targets for DENV virus replication is an essential approach in the development of new antiviral drugs. Viral infection is marked by an inflammatory process in macrophages and monocytes, which release pro-inflammatory cytokines. The release of cytokines is a trigger for the various symptoms of the disease, such as vascular leak syndrome, led by plasma leakage, fever, body pain, headache, joint pain, retro-orbital pain, neuroinflammation and hemorrhage. Natural phenolic compounds are known to inhibit dengue virus replication. Furthermore, these compounds inhibit the release of pro-inflammatory cytokines by infected cells. On the other hand, phenolic compounds do not have adequate physicochemical properties, such as Log P, which determines lipophilicity and cellular permeability. However, this research project aims to use a physical library of natural phenolic compounds obtained from agroindustry by-products, and apply the molecular modification approach. This approach proposes to modify the structure of the compounds through synthetic routes for the insertion of different chemical groups to direct improvements in the lipophilicity and cellular permeability of the phenolic compounds, as well as an increase in potency in terms of antiviral activity against DENV and inhibition of pro-inflammatory cytokines. This research project aims to identify new candidate compounds for promising antiviral drugs to inhibit the dengue virus and its inflammatory process.