Control of Fungal Diseases

The Challenge

Every year fungal disease across the world cost the agricultural industry billions in destroyed and damaged crops.  In medicine the human burden of fungal disease is comparable to TB or malaria.  There is in agriculture and medicine a problem with antifungal resistance and potential for effects of use in agriculture impacting human pathogens.

In antifungal discovery the mode of action and selectivity are vital issues determining the ultimate success of a drug or fungicide including its wider impact in toxicology studies.

The aim was to work with the agrochemical multinational company BASF as their global partner of choice in fungicide discovery which would stop the growth and/or kill the fungal disease in agricultural crops whilst not inhibiting processes within the plant.

In medicine we worked with Mycovia Pharmaceuticals to identify mode of action and selectivity for their novel candidate drug used initially for recurrent thrush. This occurs in 5-8% of women and was approved for use in April 2022. Working with Pulmocide Ltd we identified the mechanism of action of their novel chemical Opelconazole that is approved for administration directly to lungs of lung transplant patients with the life-threatening fungal disease aspergillosis.

These impacts were also supported by the ERDF BEACON project funded by Welsh Government/ EU.

The research undertaken was focussed on investigating cytochrome P450 (a superfamily of enzymes found in bacteria, fungi, plants, protozoa, animals and more recently viruses). One of these enzymes is the target of antifungal compounds for medicine and agriculture (cytochrome P45051) involved in sterol production.

Overall the design and development of a unique set of molecular cytochrome P45051 protein tools from plant pathogens has enabled a specific strategic approach for testing novel potential fungicides by BASF. This led to the discovery and development of Revysol®. With Mycovia Pharmaceuticals a potent inhibition of Candida albicans CYP51 was established and a complete lack of inhibition of human CYP51 for Oteseconazole.

Pulmocide Ltd made Swansea partner of choice to investigate mode of action of Opelconazole in Aspergillus fumigatus where Swansea had reported the only biochemical assay for CYP51A in this fungus.

The impact

• Increased broad spectrum disease control protecting yields within a remarkable 40 crops such as cereals, soy, corn, fruit and vegetables. Large impact for Global Food Security
• Commercial impact for BASF in excess of $1billion pa, being used across 60 countries in North America, South America, Europe, Middle East, Africa, Asia and Australasia
• Control of fungal infections beginning with recurrent thrush in women treated by Oteseconazole followed by further antifungal uses after more trials
• Treating life-threatening aspergillosis in lung transplant patients using Opelconazole.  This will be followed with appropriate scrutiny for use in other immunocompromised patients and other conditions where aspergillosis can occur. For example COVID-19 and aspergillosis, TB and aspergillosis, cystic fibrosis and aspergillosis, COPD and aspergillosis, allergic asthma caused by Aspergillus fumigatus
• Alongside translational research on antifungals research is antifungal antifungal resistance research in medicine and agriculture