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Tuberculosis Portfolio

from DDU Annual Report 2022

by Wellcome Centre for Anti-Infectives Research, Dundee

from DDU Annual Report 2022, page 20

Coronavirus Portfolio

The tuberculosis (TB) team aims to identify new drug candidates for progression towards clinical studies. We are focussed on identifying compounds acting on novel modes of action to complement the therapies that already exist and which offer new potential in the treatment of the disease. Multi – and extensively – drug resistant strains of TB continue to increase, so there is an urgent need to discover new drugs to overcome resistance to the front-line therapies. By targeting novel modes of action, the aim is that pre-existing clinical resistance will be reduced or non-existent. Prior to the COVID-19 pandemic, TB was the global leading cause of death due to an infectious agent. Some 10 million people are infected each year, and an estimated 1.5 million people died from TB in 2020. The extent to which the COVID-19 pandemic will have impacted TB diagnosis and treatment is yet to be established. Reduced access to healthcare during the pandemic, resulting in less TB cases being recorded is likely to set back years of progress on combatting TB. As a member of the Tuberculosis Drug Accelerator (TBDA) and European regime accelerator for new TB treatments (ERA4TB) we work with numerous academic and commercial partners across the globe towards achieving our goals.

Portfolio overview

Our efforts on TB range from hit discovery through to preclinical candidate selection. Our main areas of activity are:

→ Phenotypic screening of compound libraries against TB (more than one million compounds screened to date) through collaboration with National Institute of Allergy and Infectious Diseases (NIAID) in the USA (Prof Clifton Barry).

→ Working with partners to identify the targets of phenotypic screening.

→ Target based projects focussing on high value, novel targets.

Key highlights for 2022

→ New award from the Bill & Melinda Gates Foundation, Designed optimised leads for infectious diseases (DOLFIN), kicked-off in March 2022

→ Our work on LysS as a novel target for TB drug discovery was published doi.org/10.1038/s41467-022-33736-5

→ New hit-to-lead series displayed proof of concept in vivo efficacy

→ Completed phenotypic screening of a large 140,000 compound library in partnership with the NIH

→ Screening completed and potent hits identified for a novel TB target

“I like working in the DDU because it’s important to me that I am working on something which could literally be a lifesaver for a lot of people. I feel like our research will make a difference in people’s lives.”

Alice, Structural Biologist

“It is really rewarding to contribute towards the identification of new drugs to tackle TB. This neglected disease is a major global cause of both mortality and financial burden. But due to its ‘low profile’ within the developed world, limited efforts are focused on it from ‘mainstream’ drug discovery efforts.”