Natural compounds as antiviral candidates against human respiratory syncytial virus (hRSV)

• Grant number: 22/10481-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 17, 2023
• End date: February 16, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Fátima Pereira de Souza
• Grantee: Jéssica Maróstica de Sá
• Supervisor: Mark E. Peeples
• 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
• Institution abroad: Ohio State University, United States
• Associated to the scholarship: 20/13582-1 - Coumarins and hesperetins modified antiviral candidates for the hydrophobic pocket at the nucleoprotein/phosphoprotein interaction site of the Human Respiratory Syncytial Virus, BP.DR

Abstract

Lower respiratory tract infections (LRTI) causing bronchiolitis and pneumonia in infants and young children, are mainly caused by respiratory syncytial virus (RSV), which makes it the most frequent cause of hospitalization worldwide. Nearly all children, by the age of 2 years have been infected by hRSV. Elderly people are also very susceptible to hRSV infection making it the second most frequent cause of death in winter, after influenza virus. The distribution of hRSV is homogeneous throughout the world and causes annual outbreaks in a predictable manner each late Fall and early Winter. To date, there are no licensed vaccines or specific drugs against hRSV, with the exception of palivizumab, a monoclonal antibody that can be given to infants at high risk for severe RSV disease due to premature birth or heart defects. The Research Institute at Nationwide Children's Hospital in Columbus is one of the largest pediatric research centers in the world, where the researcher Mark Peeples is a principal investigator in the hospital Research Institute's Center for Vaccines and Immunity. He is pursuing new therapies and vaccines against hRSV. RSV infection has been primarily studied using well-differentiated human bronchial epithelial (HBE) cell cultures, as they accurately represent human airway epithelium in both appearance and function. These cultures are derived from progenitor cells extracted from donor lungs in Dr. Peeples Laboratory and differentiated over the course of 5 weeks in air-liquid interface cultures. Given the context presented, molecules of natural origin, such as flavonoids and coumarins, with antiviral properties, promote significant visibility in the pharmaceutical field, as they confer attractive characteristics for the design of new therapeutic strategies. Jéssica Maróstica de Sá, in her master's and now during her doctoral work, has been investigating through biophysical experiments, the interaction of coumarins and hesperetin with the nucleoprotein of hRSV. She intends to test the viral inhibition of these molecules in cell culture in Dr. Peeples' Laboratory, with the help of his research group. There she will also acquire knowledge and learn techniques important for the development of both vaccines and new anti-viral therapies in a setting of RSV expertise. (AU)