Study of g protein interaction from human respiratory syncytial virus with flavonoids for antiviral development

• Grant number: 15/09261-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2016
• End date: December 31, 2016
• Field of knowledge: Health Sciences - Collective Health - Epidemiology
• Principal Investigator: Fátima Pereira de Souza
• Grantee: Vitor Brassolatti Machado
• 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 the main causative agent associated with chronic respiratory diseases like bronchiolitis and especially asthma presenting analogous symptoms in patients with high-risk disease such as premature infants, elderly and immunocompromised patients. In this patients, the deleterious innate inflammatory in the lung, which links the relationship between RSV and asthma. Currently, the pathologies caused by RSV are poorly understood and the data concerning to vaccine development indicate the necessity for considerable improvement. The G glycoprotein located on the surface of human respiratory syncytial virus modulates or regulates the interaction of the virus with the host cell membrane and consequently plays a key role in the spread of the virus. Determining the identity and biophysical characterization of this protein will help to clarify the mechanism of virus - host interaction. These actions are very important to understand and to drive news designs of therapeutic or vaccine targets. Our group has succeeded in cloning and expressing the gene of the G protein of RSV. The recombinant G Protein will be tested for its interaction with quercetin and its analogues. This study will be conducted by utilizing the complementary techniques of fluorescence spectroscopy and Circular Dichroism. This proposal is based on the epidemiological scenario that calls for the maintenance of scientific efforts in the search for effective anti-RSV drugs and is associated with the experience of our group in this field. The parameters generated by the analysis of the structure of the G protein and its interaction with quercetin, may contribute to clarify various issues such as: what type of interactions between the G protein and potential inhibitors of RSV infection are important? What is the influence of these inhibitory molecules in blocking the interaction with the cell receptor? The results of this study will provide key information concerning the stability of the protein and will help characterize the site of interaction of small ligands essential for developing the interaction model and will be essential to propose efficient therapeutic models.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MACHADO, VITOR BRASSOLATTI; DE SA, JESSICA MAROSTICA; MIRANDA PRADO, ANA KARLA; DE TOLEDO, KARINA ALVES; REGASINI, LUIS OCTAVIO; DE SOUZA, FATIMA PEREIRA; CARUSO, ICARO PUTINHON; FOSSEY, MARCELO ANDRES. Biophysical and flavonoid-binding studies of the G protein ectodomain of group A human respiratory syncytial virus. HELIYON, v. 5, n. 3, MAR 2019. (16/01749-3, 15/09261-7)