Study of the effect chalcone derivatives on hRSV replication cycle in cell culture

• Grant number: 22/01492-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2022
• End date: July 31, 2024
• Field of knowledge: Health Sciences - Collective Health - Epidemiology
• Principal Investigator: Fátima Pereira de Souza
• Grantee: Jefferson de Souza Busso
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

hRSV is one of the main infectious agents that cause Acute Respiratory Infections (ARIs) worldwide, especially in children under age two, leading to severe cases of bronchiolitis and pneumonia, potentially causing sequelae. It is estimated that almost all children up to two years of age have become infected with hRSV, with 2% of these requiring hospitalization. Even though there are many vaccine candidates, it hasn't been yet one capable of creating antibodies in the long term, which keep us being dependent on a high-cost treatment, which can cause serious side effects, such as the use of the antiviral Ribavirin or antibodies such as Palivizumab, restricted to groups of risk. The search for new molecules and therapies that interfere in the replication cycle of hRSV and that are more economically accessible is necessary. Chalcone derivatives are promising candidates in the fight against the virus. They are molecules found in plants that have shown antiviral action against several infectious agents through different routes of action. This project aims to investigate the effects of chalcone derivatives on the replicative cycle of hRSV. More specifically, the objective of this project will be to investigate the effect of derivatives of kaempferol and chalcones on the phases of the replicative cycle of hRSV. Hep-2 cells will be incubated in different concentrations of derivatives of kaempferol and chalcones in virucidal action evaluation protocols, in which the phases of the viral infection cycle (adhesion, internalization, replication and budding) will be verified at the pre and posttreatment level. Those conditions which present an inhibitory effect will be used in the search for protein pathways that might be altered by derivatives of kaempferol and chalcones. We will be using Mass Spectrometry (MS) Nuclear Magnetic Resonance (NMR) to evaluate the generated metabolites and proteins. The development of this project could aid in the identification of effective compounds in the prevention and / or treatment of hRSV infections.