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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.

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

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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