Investigation of Chalcone Derivatives and NS1 Protein of hRSV in 3D Cell Culture: An Interactome-Based Approach for Antiviral Discovery

• Grant number: 24/20836-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2025
• End date: September 30, 2028
• 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

The human respiratory syncytial virus (hRSV) is a leading cause of severe acute respiratory in-fections in children under 5 years old and the elderly, often resulting in bronchiolitis and pneumonia. Globally, hRSV is estimated to cause 3.2 million infections annually, leading to around 130,000 deaths. Current treatment options are limited, with ribavirin showing limited efficacy, especially in severe cases, highlighting the need for new and more effective therapies. This project aims to investi-gate the potential of chalcone derivatives to modulate the immune response during hRSV infection, focusing on inhibiting the immunosuppressive activity of the NS1 protein, which helps the virus evade the immune system. Using 3D cell cultures supplemented with recombinant NS1 protein, the study will analyze the extracellular medium to assess the expression of pro-inflammatory cytokines, in-cluding IL-6, TNF-¿, and IFN-¿, via flow cytometry. Additionally, a temporal analysis of extracellular metabolites will be conducted using Nuclear Magnetic Resonance (NMR), combined with detailed proteomic profiling through Mass Spectrometry (MS). The findings of this research are expected to provide insights into the effects of chalcone derivatives on immune response and cellular metabo-lism during hRSV infection, potentially identifying new therapeutic targets and advancing the devel-opment of more effective antiviral and anti-inflammatory treatments against hRSV. (AU)