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Leuven researchers develop treatment against dengue fever

14:21 08/10/2021

It's not every day that a university team discovers a new antiviral against a devastating virus. While the world still awaits a miracle pill to wipe out SARS-CoV-2, the University of Leuven seems well on the way to developing an oral drug against dengue fever, a tropical disease transmitted by mosquitoes.

The discovery of this antiviral is the result of 12 years of work, a collaboration between researchers from the Institute Rega and CD3 (the Centre for Drug Design and Discovery). The results have been published in the journal Nature.

Dengue is present in almost all tropical regions, but especially in Latin America and Asia. This virus, transmitted by mosquitoes, infects up to 400 million people each year. Up to 100 million people are sick with it, and thousands die.

High fever and severe pain in muscles and joints are common symptoms, which are sometimes accompanied by bleeding under the skin or capillary exudate (leakage of substances out of the blood vessels). And with climate change, the mosquito is expanding its range.

This antiviral does not prevent the virus from entering the cell, but it prevents it from replicating. It was tested on mice and the number of viral particles in the blood dropped within 24 hours of starting treatment, even though the peak of infection had already been reached.

Professor Johan Neyts, from the Rega Institute at KU Leuven, worked in collaboration with a research team from the University of Heidelberg.
“Our inhibitor prevents the interaction between two viral proteins that are part of a sort of photocopier of the genetic material of the virus,” he said.

“Blocking this interaction prevents the virus from copying its genetic material. The result is that no more new virus particles are produced.” Additionally this antiviral appears to be very effective against all variants of the dengue virus known to date.

The Leuven team first examined several thousand molecules in a chemical library at the Centre for Drug Design and Discovery to find one or more molecules capable of inhibiting the virus in cells produced in the laboratory.

It was able to identify potential targets, and chemists began to work on these molecules, of which they created different versions. The optimisation process took nearly 2,000 steps, leading to a dengue inhibitor that the team touts as ultra-powerful.

Janssen Pharmaceuticals has joined forces with the Leuven teams to continue clinical trials, this time on humans.

Written by Richard Harris