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27 April 2023

Technique opens up potential for producing new antivirals

King’s researchers have developed a new technique that allows them to identify novel, naturally occurring antiviral molecules that could be used to help combat future viral pandemics.

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Led by Dr Ebrahimi Kourosh, the researchers developed a new, simple, in vivo technique called the VITAS assay that allows them to identify enzymes involved in the production of antivirals. The study highlights how the assay was able to analyse the enzymes from human, fungi and bacterial cells and identify the ones with antiviral activity.

As the rise of viral infections including HIV-1, Ebola and most pertinently SARS-CoV-2, researchers have long been interested in developing new broad-spectrum antiviral drugs blocking viral reproduction machinery. One area of focus has been natural products from organisms; these are molecules produced by nature’s biocatalysts (enzymes) to support their growth, maintenance, reproduction, or defence.

Though techniques already exist that can test these natural products, they require the production and purification of enzymes within the laboratory. This makes it incredibly difficult to efficiently screen a vast range of enzymes and natural products. In contrast, the VITAS assay is based on a signal to cause cell death when an antiviral molecule is not produced by an enzyme candidate.

Dr Kourosh’s study shows that VITAS is able to mine a range of enzymes and select the correct candidates that displayed antiviral activity as an in vivo technique based on cell survival – i.e. one that can be performed using live microorganism. It will now be easier to select and identify a broad range of enzymes – an important step in producing the subsequent antiviral products.

VITAS is a simple and sensitive in vivo assay to mine the repository of natural and engineered enzymes and discover those with antiviral activity. It will support our efforts to decode an evolutionary conserved antiviral defence system and develop radically new antiviral therapeutic biotechnologies.

Dr Kourosh H. Ebrahimi, Lecturer in Immunology & Drug Discovery

Following this research, Dr Kourosh Ebrahimi has received a £70,000 grant from the Royal Society to purchase a liquid chromatography-mass spectrometry (LC-MS) system that, combined with the VITAS assay, will allow his team to screen enzymes producing antivirals.

Read the full study published in Chemical Communications.

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Lecturer in Immunology and Drug Discovery