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New AntiBacterials with Inhibitory activity on Aminoacyl-tRNA Synthetases

Objective

The NABARSI consortium will develop a cutting-edge drug discovery project to increase the antibacterial pipeline. The main goal of NABARSI is to find new chemical entities (NCEs) with antibacterial efficacy in animal models of multi-drug resistant (MDR) bacterial infection and to exploit the results through obtaining a co-development with industry. The NABARSI consortium consists of 5 partners: Omnia Molecular (Omnia, SME; Spain). InhibOx (SME, UK). Latvian Institute of Organic Synthesis (LIOS, Latvia), Leeds University (Leeds, UK) and Erasmus Medical Centre (ErasmusMC, The Netherlands - Coordinator).
Antibacterial activity will be achieved through inhibition of essential aminoacyl-tRNA synthetases (aaRS). Individual aaRS are highly conserved across bacteria, enabling the discovery of broad-spectrum antibacterials. To reduce the likelihood of resistance, NABARSI will look for NCEs with inhibitory activity against multiple aaRS enzymes. InhibOx and LIOS will design NCEs by rational and fragment based drug discovery methods followed by synthetic structure optimization. To increase chemical diversity, virtual screening of large (>100 M) compound libraries available at InhibOx will be performed. Limitations of previous aaRS inhibitors will be overcome by novel approaches such as the In Omnia assay: activity of the compounds on pathogenic aaRS enzyme is measured inside a human cell, allowing rejection of compounds acting through human aaRS and identifying compounds that cross biological membranes. The expertise of Leeds in mode of action studies will be used at an early stage. Activity of the NCEs on clinical isolates of MDR strains available at ErasmusMC will be assessed. Resistance appearance frequency and mechanisms will also be assessed early by selection and characterization of resistant mutants by ErasmusMC and Leeds. A co-development agreement with pharmaceutical companies will be intensively sought with the aim of exploiting the NCEs upon finalisation of NABARSI.

Field of science

  • /natural sciences/chemical sciences/electrochemistry/bioelectrochemistry/electroporation
  • /medical and health sciences/basic medicine/pharmacology and pharmacy/drug resistance/multidrug resistance
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes

Call for proposal

FP7-HEALTH-2013-INNOVATION-2
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Address
Dr Molewaterplein 40
3015 GD Rotterdam
Netherlands
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 615 368,86
Administrative Contact
John Hays (Dr.)

Participants (4)

OXFORD DRUG DESIGN LIMITED
United Kingdom
EU contribution
€ 1 025 999
Address
The Walbrook Building 25 Walbrook
EC4N 8AF London
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Paul Finn (Dr.)
LATVIJAS ORGANISKAS SINTEZES INSTITUTS
Latvia
EU contribution
€ 885 474,69
Address
Aizkraukles 21
1006 Riga
Activity type
Research Organisations
Administrative Contact
Dace Karkle (Ms.)
UNIVERSITY OF LEEDS
United Kingdom
EU contribution
€ 758 180,72
Address
Woodhouse Lane
LS2 9JT Leeds
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Martin Hamilton (Mr.)
OMNIA MOLECULAR S.L.

Participation ended

Spain
EU contribution
€ 817 134,23
Address
Calle Josep Samitier - Parc Cientific De Barcelona 1-5
08028 Barcelona
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Lluis Ribas De Pouplana (Dr.)