Hundreds of dual-stage antimalarial molecules discovered by a functional gametocyte screen

Plasmodium falciparum stage V gametocytes are responsible for parasite transmission, and drugs targeting this stage are needed to support malaria elimination. We here screen the Tres Cantos Antimalarial Set (TCAMS) using the previously developed P. falciparum female gametocyte activation assay ( Pf FGAA), which assesses stage V female gametocyte viability and functionality using Pf s25 expression. We identify over 400 compounds with activities 10,000 compounds against stage V female gametocytes, identify active compounds belonging to 57 chemotypes and confirm transmission blocking activity of four selected compounds in vitro .