Development of Targeted Transmission-Blocking Agents Against Malaria

Lyn-Marie Birkholtz of the University of Pretoria in South Africa will identify gametocytocidal
compounds that specifically prevent human-to-mosquito transmission of gametocytes and block gamete and oocyst formation in mosquitoes as a complementary strategy to help eliminate malaria. Traditionally, anti-malarial compounds have been developed to target asexual blood-stage parasites. However, also blocking parasite transmission is critical for eradication. They developed a platform that can screen multiple sexual stages of the parasite and recently used it to identify ten hit compounds from the Medicines for Malaria Venture (MMV) Pandemic Response Box (PRB), most of which have not previously been tested against malaria-causing parasites. They will validate those hits, optimize them, and analyze their structure-activity-relationship (SAR) and their potential mode of action to identify at least one chemotype as an early lead candidate for further development.