Can de novo designed protein binders inhibit the growth of P. falciparum malaria parasites?

Despite the recent release of two vaccines, malaria remains a significant health challenge, particularly in Africa. Efforts to target the blood stage of the parasite infection have led to the discovery of neutralizing antibodies against PfRH5, a protein essential for the invasion of red blood cells (RBCs). However, in vivo, antibody titres are often too low to effectively clear the infection.

Recent advances in bioinformatics have enabled the development of machine learning models, capable of de novo design of proteins, with remarkable success rates. These tools can generate proteins that bind with high specificity to designated targets, mimicking or even surpassing the binding capabilities of natural antibodies. In this Master thesis project, these tools have been used to design proteins targeting PfRH5 on the same domain as the neutralizing antibodies