Progress new assets (one pre-new molecular entity and one first-time-in-human start) for tuberculosis that act synergistically with bedaquiline, cytochrome bc or cytochrome bd inhibitors

Projektinformationen

RespiriTB

ID Finanzhilfevereinbarung: 853903

DOI

10.3030/853903

EK-Unterschriftsdatum 8 Mai 2019

Startdatum 1 Mai 2019

Enddatum 30 April 2027

Finanziert unter

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Gesamtkosten

€ 10 062 900,01

EU-Beitrag

€ 6 840 000,00

Koordiniert durch

ACADEMISCH ZIEKENHUIS LEIDEN
Netherlands

CORDIS bietet Links zu öffentlichen Ergebnissen und Veröffentlichungen von HORIZONT-Projekten.

Links zu Ergebnissen und Veröffentlichungen von RP7-Projekten sowie Links zu einigen Typen spezifischer Ergebnisse wie Datensätzen und Software werden dynamisch von OpenAIRE abgerufen.

Leistungen

Documents, reports (9)

Enzymatic Assay and Characterization of cyt bc1 & bd inhibitors report

The Enzymatic Assay and Characterization of cyt bc1 & bd inhibitors report will describe the assay, conditions and characterisation methodology of the enzymatic assay for testing cytochrome bc1 and cytochrome bd inhibitors.

In vitro activity report for new anti-bacterial compounds

The In vitro activity report for new anti-bacterial compounds will summarize the results of in vitro activity of newly identified compounds within the project against intracellular (MDR)-Mtb strains in human cells.

Purified Mtb cytochrome report

The Purified Mtb cytochrome report will describe the methodology and confirmation of the purified cytochrome bc1, bc1:aa3, and bd

Continuous enzymatic assay and screening report

The continuous enzymatic assay and screening report will describe the assay, conditions and characterisation methodology of the continuous enzymatic assay for testing Mtr inhibitors and the application in the High Throughput Screening campaign.

Decision on final compound FiH

Short summary and scientific explanation on the final decision of the compound that will be used in the FiH. Minutes of the steering committee meeting where this will be decided are included.

In vitro synergy report for current and new anti-bacterial compounds

The in vitro synergy report for current and new anti-bacterial compounds will summarize the results of in vitro synergy between antibiotics currently used in standard TB treatment regimens and newly identified anti-bacterial compounds against intracellular (MDR)-Mtb strains in human cells.

Structures of cytochrome report

The Structure of cytochrome report will describe the structures revealed by Structural Biology of cytochrome bc1 and/or bc1:aa3 or bd.

HDT Target Identification and mode of action report

The HDT Target Identification and mode of action report will describe the process, the methodology and summarize the identified of targets and mode of actions of lead Host Directed Therapeutics compounds.

In vitro activity of single HDT compounds report

In vitro activity of single HDT compounds report will summarize the results of in vitro activity of single Host Directed Therapeutics compounds against intracellular MDRMtb strains in human cells

Websites, patent fillings, videos etc. (1)

Website RespiriTB online

The website developed for communication of all RespiriTB activities will be active and online.

Veröffentlichungen

Peer reviewed articles (3)

Host and bacterial lipid metabolism during tuberculosis infections: possibilities to synergise host- and bacteria-directed therapies

Autoren: Teun van der Klugt, Robin H. G. A. van den Biggelaar, Anno Saris
Veröffentlicht in: Critical Reviews in Microbiology, Ausgabe 51, 2025, Seite(n) 463-483, ISSN 1040-841X
Herausgeber: Taylor & Francis
DOI: 10.1080/1040841x.2024.2370979

Structural and mechanistic study of a novel inhibitor analogue of M. tuberculosis cytochrome bc1:aa3

Autoren: Amit K. Verma, Robbert Q. Kim, Dirk A. Lamprecht, Clara Aguilar-Pérez, Sarah Wong, Nicolas Veziris, Alexandra Aubry, José M. Bartolomé-Nebreda, Rodrigo J. Carbajo, Jennefer Wetzel, Meindert H. Lamers
Veröffentlicht in: npj Drug Discovery, Ausgabe 2, 2025, ISSN 3005-1452
Herausgeber: Springer Science and Business Media LLC
DOI: 10.1038/s44386-025-00008-3

A high-throughput target-based screening approach for the identification and assessment of <i>Mycobacterium tuberculosis</i> mycothione reductase inhibitors

Autoren: Natalia Smiejkowska, Lauren Oorts, Kevin Van Calster, Linda De Vooght, Rob Geens, Henri-Philippe Mattelaer, Koen Augustyns, Sergei V. Strelkov, Dirk Lamprecht, Koen Temmerman, Yann G.-J. Sterckx, Davie Cappoen, Paul Cos
Veröffentlicht in: Microbiology Spectrum, Ausgabe 12, 2024, ISSN 2165-0497
Herausgeber: American Society for Microbiology
DOI: 10.1128/spectrum.03723-23

Non-peer reviewed articles (1)

Host‐directed therapy to combat mycobacterial infections*

Autoren: Gül Kilinç, Anno Saris, Tom H. M. Ottenhoff, Mariëlle C. Haks
Veröffentlicht in: Immunological Reviews, Ausgabe 301/1, 2021, Seite(n) 62-83, ISSN 0105-2896
Herausgeber: Blackwell Publishing Inc.
DOI: 10.1111/imr.12951