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EV-2C SIGNED

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

Total Cost €

0

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.

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

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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