Rational design, computational, and in vivo strategies to combat drug-resistant Plasmodium vivax

In low-income countries, about 200 million people are infected with malaria.

In the absence of efficient malaria vaccines, the globally rising drug resistance in Plasmodium parasites necessitates new antiplasmodial drug discovery.

The COVID19 epidemic drains resources from the fight against malaria, further aggravating the situation for years to come.P. vivax establishes chronic infections through its dormant stage in the host liver.

This makes it difficult to control, and also puts a great burden on afflicted populations because of the lengthy infections. Development of drugs against P. vivax has been lagging, as no experimentally tractable life cycle phase exists. Consequently, antimalarial drugs with few exceptions target P. falciparum.

Our goal is to find drug candidates blocking the P. vivax dormant liver stage.Antiparasitic drug discovery has been slow because of insufficient funding, and inefficient scientific approaches.

We will speed this up using modern genomics-oriented technologies in target identification and drug candidate discovery. Surrogate genetics in yeast allows us to access target proteins from the dormant liver stage.

AI approaches in virtual screening and robotics in physical screening accelerate finding small molecule drug candidates.

These will be refined with medicinal chemistry and tested for efficacy against parasites resistant to existing drugs, and against the dormant liver stage in a newly designed liver model system for Plasmodium infections.