Design and peptides analogues synthesis of the SARS-CoV-2 fusion peptide for the analysis of the modulation of calcium binding in its fusogenic capacity

• Grant number: 20/15659-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2021
• End date: January 31, 2022
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Eduardo Festozo Vicente
• Grantee: Matheus Marchetti Melo
• Host Institution: Faculdade de Ciências e Engenharia. Universidade Estadual Paulista (UNESP). Campus de Tupã. Tupã , SP, Brazil

Abstract

Covid-19 has been classified as a global pandemic, the search for new effective antiviral methods has become a priority worldwide. Currently, the most efficient forms of treatment to combat the disease are the use of mechanical ventilators for cases of severe respiratory deficiencies, present in more advanced stages of the disease. Even today, prevention remains the best option to avoid contagion with the virus, since COVID-19 can be transmitted through body fluids and excretions that spread quickly through the air, increasing levels of contagion. The infection process of the new coronavirus is mediated by the Spike protein, responsible for the fusion of the viral lipid envelope with the cell membranes. The fusion occurs through the interaction with membranes of the so-called fusion peptide, a relatively hydrophobic and highly conserved amino acid segment of the Spike protein within the Coronaviridae family, which is essential for the virus's fusogenic activity. It has been hypothesized that the coordination of calcium ions at peptide sites is essential for the binding of the peptide to the target membranes and, consequently, for its function. Thus, in this project, the importance of calcium ions in the modulation of fusogenic activity and the conformation of the fusion peptide, one of the main agents for the fusion of the SARS-CoV-2 virus, will be studied. With the synthesis of the wild type fusion peptide and analogues of this peptide containing strategic substitutions in the positions where coordination with the calcium ions possibly occurs, it is intended to investigate, via biophysical studies, the specific interactions of the fusion peptide and membranes in the presence of calcium ions. (AU)