Novel validated dengue assays for drug development
Screening for compounds with viral protease inhibition activity is an important step towards the development of novel anti-infectives against dengue and flaviviruses in general. This project establishes a collaboration between Protinhi Therapeutics and Prof. Christian Klein at Heidelberg University to develop a validated dual screening assay to optimize dengue drug discovery and development.
The need for antiviral therapies against emerging infectious diseases by flaviviruses is urgent. To date, dengue virus is the most rapidly spreading and biggest viral threat with a 30-fold increase in global incidence over the past 50 years. Annually several hundred million people worldwide are infected with dengue of which between 35 and 60 million should be treated therapeutically. It is estimated that every year 500,000 people require hospitalisation due to severe dengue. A fraction of these (2.5%) become fatal. There is no specific therapy available for dengue and vaccine development has been proven difficult. The development of small-molecule antiviral drugs is also challenging, illustrated by the fact that major pharmaceutical companies and academic groups have spent substantial resources to identify effective small molecule drugs against dengue without success.
Protinhi Therapeutics designs and synthesises a novel type of compounds that directly inhibit dengue virus replication by binding to the viral protease. The Medicinal Chemistry group of Heidelberg University has extensive experience with biochemical and cellular assays for flaviviral proteases. Optimisation, upscaling and combination of two dengue protease screening assays to increase predictiveness for the eventual effect of Protinhi’s compounds is a critical step to identify lead compounds that can be developed into novel antiviral therapies.
The research proposed in this project will provide a novel screening basis for antiviral strategies against future emerging flavivirus infections, thereby alleviating the disease burden in future outbreaks of flaviviruses such as dengue, Zika and West Nile fever.
