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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.

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

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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