CHIKV-FBDD
Financiado
Structural investigation into functionality of Chikungunya virus nsP2 in replica...
Structural investigation into functionality of Chikungunya virus nsP2 in replication complex and screening of small molecules for its inhibition
Chikungunya virus (CHIKV) is a medically important pathogen that affected millions of people around the world. CHIKV
infection causes high fever, intense joint pain and often leads to chronic virus-induced arthritis, thus there i...
Chikungunya virus (CHIKV) is a medically important pathogen that affected millions of people around the world. CHIKV
infection causes high fever, intense joint pain and often leads to chronic virus-induced arthritis, thus there is a clear necessity
to develop antiviral compounds capable of eliminating persisting virus. CHIKV is an alphavirus from Togaviridae family with
single-stranded positive-sense RNA genome, which replication is carried out by a complex of four viral non-structural (ns)
proteins, initially produced in a form of ns-polyprotein precursor and released by proteolytic processing. Because
multifunctional nsP2 plays a central role in a replication cycle of CHIKV by exhibiting various enzymatic activities and
counteracting cellular defence mechanisms, it represents the most attractive target for drug design and screening. Currently,
the structural information regarding CHIKV ns-proteins is limited, whereas the platforms for in vitro testing the potential
inhibitors are largely non-existent. Therefore the first aims of this project will be to apply structural biology approaches to
elucidate spatial organization of nsP2 and to reveal its contacts with other ns-proteins in the replication complex.
The druggability of nsP2 will be then explored by screening recombinant proteins against libraries of chemical fragments and
characterizing binding of small molecules using sensitive biophysical techniques and crystallographic analysis. The potential
of selected compounds to interfere with enzymatic or interaction properties of nsP2 will be revealed using variety of
fluorescence-based assays developed in this project. The newly discovered knowledge about structural features of CHIKV
nsP2, identification of novel protein surface pockets and binding molecules, and the development of functional assays for the
analysis of their inhibitory potential are expected to create the ground for future elaboration of novel specific inhibitors of
CHIKV.
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Duración del proyecto: 26 meses
Fecha Inicio: 2016-03-17
Fecha Fin: 2018-06-06
Fecha Fin: 2018-06-06
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2018-06-06
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
MSCA-IF-2015-EF:
Marie Skłodowska-Curie Individual Fellowships (IF-EF)
Cerrada
hace 9 años
Presupuesto
El presupuesto total del proyecto asciende a
195K€
Líder del proyecto
THE CHANCELLOR MASTERS AND SCHOLARS OF THE UN...
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Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
287.94K€ |
Participante