ViralFP

Project Title
Using computational and experimental methods to provide a global characterization of viral fusion peptides
Project Type
Nacional / Public
Funding Body
Funding Program
02/SAICT/2017 - Projetos de Investigação Científica e Desenvolvimento Tecnológico (IC&DT)
Reference
NORTE-01-0145-FEDER-028200
Funding
  • CEB: 17 900,00
  • Total: 239 648,00
Start
01-10-2018
End
30-09-2021
Partnership
UNL, UMinho, IMM

Principal Investigator

Abstract

The fusion peptide (FP) is determinant for the infection process of enveloped virus, which include major pathogens such as HIV, dengue and Ebola. This peptide, located within the fusion protein, inserts into the host membrane and promotes fusion between the viral and host membrane, which is essential the infection process. FPs are very promising therapeutic targets and, therefore, there is a tremendous interest in identifying these peptides and characterizing their properties. FPs from different viral families are quite distinct at the sequence and structural level, although they are all hydrophobic tend to have high Ala and Gly contents. In some cases (e.g. influenza, HIV and parainfluenza) the FP corresponds to the N-ter end of the fusion protein, whereas in other cases (e.g. dengue) it is internalized. This raises an important question: How can peptides with such distinct features execute the same function? The long-term goal of this project is to shed light into this matter and provide a general perspective of the role of viral fusion peptides in membrane fusion, using a combination of computational and experimental methods. This knowledge will be crucial for the development of therapeutics targeting fight both human and animal infections. The project has two main objectives: - Elucidate how FPs from different viral families interact with the host membrane and promote fusion - Develop computational tools to find the patterns that characterize viral FPs, which will enable the identification of unknown FPs project is divided in three tasks: 1- Simulation of fusion peptides belonging to different families In this task we will use state-of-the-art simulation methods analyse FPs belonging to two different virus families (Paramyxoviridae and Flaviviridae). The aim is to elucidate how different FPs interact with the membrane, pinpoint important residues and determine which are the structural and physicochemical features that control the FP-membrane interaction. Experimental analysis of fusion peptides belonging to different families The aim of this task is to provide experimental support for the results obtained 1, by analysing the same systems using several biophysical techniques. 3- Development of computational tools to identify and characterize viral fusion peptides In this task, we will integrate all the available information on viral FPs in a web platform and develop a machine-learning algorithm to find the patterns that characterize them. This algorithm will be able to identify novel FPs and it will be publicly available in the web platform. This project will provide an important contribution to elucidate the role of FPs in membrane fusion, which will provide hints for the development of antiviral drugs and vaccines. these peptides are crucial for the infection process of some of the most important human and animal pathogenic virus, this work is expect to have a high social impact.