Enzyme may be key to safer drugs against black fever

A new screening system developed at the University of Durham, UK, may help develop safer drugs against the tropical disease Leishmaniasis, also known as black fever, according to the World
Health Organisation (WHO), about 12 million people worldwide are infected by the parasite every year. Many of the drugs used to treat this potentially deadly disease have toxic side-effects,
killing one in 10 patients.

Trying to gain new insights into the biochemical processes at play, the Durham researchers have discovered a key enzyme which helps produce an essential cell component of the single-celled
microbe or protozoan causing the disease. What is more, they found an inhibitor which acts against this particular enzyme.

‘Identifying both the enzyme responsible […] plus the inhibitor which acts against the enzyme is very significant,’ research leader Dr Paul Denny pointed out. ‘It has marked implications in
the search for anti-protozoan drugs with reduced side-effects.’ Knowing how to block the enzyme could help prevent the protozoa from establishing infection, Dr Denny added.

The biochemical processes of the microbe and its human host are very similar, so that it has been impossible to develop safer drugs. But that may be about to change. ‘Potentially we can rapidly
screen thousands of compounds for inhibitory effects against this enzyme’, Dr Denny said. ‘It provides a much quicker means of identifying inhibitors with the potential for drug development
than is standardly used.

‘Leishmaniasis is an extremely damaging disease which threatens 350 million people in 88 countries around the world,’ Professor Nigel Brown from the Biotechnology and Biological Sciences
Research Council (BBSRC), which supported this study, commented. ‘This research demonstrates how important fundamental bioscience research is to developing life-saving pharmaceuticals, and
should provide hope to people in affected regions.’

Leishmaniasis is mainly found in tropical regions of Central and South America, Asia, the Middle East and Africa, but also in southern Europe. Mostly, it is transmitted by sand flies. However,
more recent cases have been reported in Europe amongst intravenous drug users with human immunodeficiency virus (HIV).

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