Virucidal Mechanism of Action of Jaceosidin Against hRSV: Focus on the Interaction with the F Protein

• Grant number: 25/16306-9
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: December 01, 2025
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Karina Alves de Toledo
• Grantee: Isabelly Gonzaga de Jesus
• Supervisor: Diana Andreia Pereira Lousa
• Host Institution: Faculdade de Ciências e Letras (FCL-ASSIS). Universidade Estadual Paulista (UNESP). Campus de Assis. Assis , SP, Brazil
• Institution abroad: Universidade Nova de Lisboa, Portugal
• Associated to the scholarship: 24/03514-0 - Evaluation of the mechanisms by which Jaceosidin and Kaempferol 7 O-neohesperidoside inhibit the replication of Human Respiratory Syncytial Virus (hRSV)., BP.IC

Abstract

The Human Respiratory Syncytial Virus (hRSV) is one of the leading causes of severe respiratory infections in children, the elderly, and immunocompromised individuals, resulting in high morbidity and mortality rates. Current prophylactic and therapeutic options (Ribavirin, monoclonal antibodies, and vaccines) remain limited in terms of efficacy, accessibility, and coverage for at-risk groups. Our research group has been investigating the antiviral potential of natural compounds against hRSV. Previous studies (FAPESP 2023/02743-2) demonstrated that the flavonoids Jaceosidin and Kaempferol 7-O-neohesperidoside exhibit in vitro antiviral activity. However, only Jaceosidin showed efficacy in virucidal treatment, suggesting a direct interaction between this flavonoid and the hRSV viral particle. Continuation of the research (FAPESP 2024/03514-0) revealed that Jaceosidin's mechanism of action focuses on the viral adhesion step, inhibiting more than 50% of hRSV particle attachment to the membrane of Hep-2 cells. Plaque formation assays confirmed these findings. Taken together, these results indicate that Jaceosidin, like other previously studied flavonoids, may interact with the viral F protein, which is primarily responsible for the early stages of hRSV cell infection. The current proposal aims to investigate the interaction between the hRSV F protein and the flavonoid Jaceosidin through both in vitro and in silico approaches. This study will be conducted during a BEPE internship in collaboration with researchers at Universidade Nova de Lisboa, Portugal. Interaction analyses between recombinant F protein and commercially obtained Jaceosidin will be performed, allowing the determination of parameters such as the thermodynamic affinity constant. In parallel, computational analyses will be carried out using molecular docking methodologies and molecular dynamics simulations to characterize the molecular details of the interaction between the two molecules. The data generated will complement our group's previous research and may guide new strategies for the treatment of patients with hRSV. (AU)