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EV-2C SIGNED

Structural and functional studies of enterovirus 2C proteins: promising targets for antiviral therapy.

Total Cost €

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EC-Contrib. €

0

Partnership

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 EV-2C project word cloud

Explore the words cloud of the EV-2C project. It provides you a very rough idea of what is the project "EV-2C" about.

genome    alter    encapsidation    viral    urgent    aaa    ev    host    lifecycle    generate    enterovirus    vivo    map    sepsis    2c    situ    proteins    spectrum    hijack    effect    d68    cooperatively    tomography    functions    vp1    structure    search    inhibitor    atpase    attractive    hexameric    ligand    characterise    encodes    positive    drugs    sought    enteroviruses    broad    genomes    array    viruses    organelles    ranging    mutations    structural    virus    pathogens    diseases    functional    cellular    requirement    interactions    disparate    hundreds    protein    anti    shed    sequence    poliovirus    structurally    mild    microscopy    platforms    light    membranous    enteroviral    template    sense    life    urgently    rhinoviruses    resistance    genus    paralysis    electron    cryo    homeostasis    3a    a71    complexes    resolution    2a    neonatal    seven    membranes    molecular    helicase    drug    lipid    coxsackieviruses    threatening    responsible    conservation    vaccination    organisation    morphogenesis    ssrna    2b    ex    cell    comprise    human    option    replication    basis    antivirals    virion    cycle    serve    reorganisation   

Project "EV-2C" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITEIT UTRECHT 

Organization address
address: HEIDELBERGLAAN 8
city: UTRECHT
postcode: 3584 CS
website: www.uu.nl

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Netherlands [NL]
 Total cost 175˙572 €
 EC max contribution 175˙572 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2019
 Duration (year-month-day) from 2019-04-01   to  2021-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITEIT UTRECHT NL (UTRECHT) coordinator 175˙572.00

Map

 Project objective

The enterovirus (EV) genus comprises many important human pathogens including poliovirus, coxsackieviruses, EV-A71, EV-D68 and rhinoviruses. These viruses are responsible for a wide array of diseases ranging from mild to life-threatening, such as neonatal sepsis and paralysis. There are hundreds of enteroviruses, and vaccination to all of these is not a viable option. As such, there is an urgent requirement for effective broad-spectrum antivirals.

Enterovirus genomes comprise a positive-sense ssRNA genome which encodes four structural proteins (VP1--4) and seven non-structural proteins (2A--C, 3A--D). The non-structural proteins 2B, 2C and 3A cooperatively hijack host cell proteins and alter host cell membranes and lipid homeostasis to generate membranous replication organelles, which serve as platforms for genome replication and virion morphogenesis.

The 2C protein is a particularly attractive target for the development of antivirals due to its high level of sequence conservation. 2C is an AAA ATPase with many proposed functions within the virus lifecycle including helicase activity, reorganisation of cellular membranes and encapsidation. Several structurally disparate drugs target 2C on the basis that resistance mutations map to this protein; however, the molecular basis of their effect on 2C is not understood.

This project has two main objectives: 1. Determine the high-resolution structure of the functional hexameric 2C and inhibitor/ligand complexes by cryo-electron microscopy. 2. Use cryo-electron tomography to characterise the interactions 2C makes with viral and host proteins within ex-vivo and in situ replication organelles.

Understanding the organisation of 2C within replication organelles will shed new light on its role in the enterovirus life cycle, and the high-resolution structure of 2C will serve as a long sought-after search template for structure-based drug design of urgently-needed anti-enteroviral drugs.

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The information about "EV-2C" are provided by the European Opendata Portal: CORDIS opendata.

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