Informace o projektu

Structural studies of human picornaviruses directed towards development of anti-viral compounds (PicoDrugs)

Logo poskytovatele
Kód projektu
335855
Období řešení
3/2014 - 2/2019
Investor / Programový rámec / typ projektu
Evropská unie
Fakulta / Pracoviště MU
Středoevropský technologický institut

Many picornaviruses are human pathogens that cause diseases varying in
symptoms from common cold to life-threatening encephalitis. Currently
there are no anti-picornavirus drugs approved for human use. We propose to study molecular structures of picornaviruses and their life cycle
intermediates in order to identify new targets for anti-viral inhibitors
and to lay the foundations for structure-based development of drugs
against previously structurally uncharacterized picornaviruses.
We will use X-ray crystallography to determine virion structures of
representative viruses from Parechovirus, Kobuvirus, Cardiovirus, and
Cosavirus genera and Human Rhinovirus-C species. We will use cryo-electron microscopy to study picornavirus replication complexes in order to explain the mechanism of copy-choice recombination of picornavirus RNA genomes that leads to creation of new picornavirus species. We will determine whether picornavirus virions assemble from capsid protein protomers around the condensed genome or if the genome is packaged into a pre-formed empty capsid. Furthermore, we will investigate how picornaviruses initiate infection by analyzing genome release from virions and its translocation across lipid membrane. A major innovation in our approach will be the use of focused ion beam micromachining for sample preparation that will allow us to study macromolecular complexes within infected mammalian cells by cryo-electron tomography. Our analysis of virion structure, cell entry, genome replication, and particle assembly will identify molecular details and mechanism of function of critical picornavirus life-cycle intermediates.

Publikace

Počet publikací: 3


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