Novel Small Molecule Antimalarials for Elimination of Malaria Transmission

The transmission of malaria begins with injection of sporozoites into a human from the bite of a female anopheles mosquito, which initiates the malarial life cycle in humans. When a mosquito bites an infected human, the ingested male and female malaria gametocytes fuse to form a zygote that eventually becomes an oocyst. Each oocyst produces thousands of sporozoites which migrate to the mosquito salivary glands, ready to infect a new human host.

Currently, the available therapeutics for malaria can effectively eliminate the asexual stages of malarial parasites that cause clinical symptoms in patients. However, their abilities to eliminate the gametocyte (sexual stage of the parasites) as well as the liver stage parasites are limited. The subject technology involves novel compounds, which include Torin 2, that are potently gametocytocidal in in vitro assays and in a mouse model of malaria, completely blocked the host-to-mosquito transmission by suppressing oocytes formation in mosquitoes.