Novel antifungals to treat resistant organisms (NOFUN)

This project brings together leading European SME’s and academics to address the rising trend of antimicrobial resistant fungi through the development of novel classes of antifungals and the identification of novel drug targets.

Aspergillus fumigatus. Image provided by Universitat Rovira i Virgilli.

Project Background

About 1.7 billion people worldwide are afflicted by fungal diseases. The majority of these infections are superficial; however, a significant proportion are invasive. Due to their pathology and masking by primary infections, invasive fungal infections are both difficult to diagnose and treat. This can lead to an estimated 1.5 million deaths each year. This exceeds mortality estimates for either tuberculosis or malaria.

The majority of invasive infections are caused by species belonging to four genera, Aspergillus, Candida, Cryptococcus and Pneumocystis. Worryingly, where diagnosis is successful, a growing and significant proportion of fungal infections are classified as being ‘Antimicrobial Resistant’ (AMR). There is a desperate need for new antifungal drugs before the limited number of antifungal agents are rendered ineffective.

Over the last decade, Europe has led the world in describing the extent and mechanisms of antifungal resistance, which has emerged as a current and growing threat to the European population. The azole class of antifungal agent is by far the most dominant class of agent used to treat fungal disease in man. Resistance of Aspergillus fumigatus to the azoles is becoming a major problem in Europe and is being driven by two factors, the prolonged exposure (several months to several years) of patients to azoles and the extensive use of agricultural azoles driving environmental resistance.

Consortium

The NOFUN consortium has identified potent novel broad-spectrum antifungal molecules that are active against multi-resistant fungal pathogens and intends to qualify these as drug candidates. One of these assets is already at the lead identification stage. Cutting edge fungal genomics will be used to identify novel drug targets and advance these to develop qualified tractable chemical inhibitors. With their wide ranging expertise across medicinal chemistry, ADMET, fungal biology, chemical genomics and drug development, the consortium partners will build and progress a broad pipeline of agents that have the potential to reach the clinic within 5 years.

Identifying new cellular targets