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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.

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

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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