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Malaria breakthrough. A collaboration between ISS, IRBM and CNR has led to the discovery of new molecules blocking the transmission of the parasite

Iss, june 8th 2022 - The Istituto Superiore di Sanità, IRBM and CNR today announced collaborative research published in the journal Communications Biology (doi: 10.1038/s42003-022-03510-w) that identified new molecules which block the transmission of the malaria parasite from an infected person to the mosquito, the first step in developing new drugs to eliminate this major infectious disease.

In response to the guidance of the World Health Organization to attack the malaria parasite on multiple fronts, researchers have collaborated, in recent years, in the search for new molecules able to block the transmission of the most dangerous of malarial parasites, Plasmodium falciparum - a project funded by the public-private consortium CNCCS, formed by CNR, ISS and IRBM.

This work identified seven molecular structures (chemotypes), three of which have never been identified in the past, able to kill gametocytes and prevent the development of the parasite in the mosquito.

The success of this work was possible thanks to the combination of biological knowledge on the parasite stages transmissible to the Anopheles mosquito (the gametocytes), innovative cell-based assays on transgenic parasites and the expertise in large-scale screening of pharmacologically active compounds.

Giacomo Paonessa, Group Leader at IRBM, outlined that "the biological assay funnel developed in this collaboration was able to efficiently and quickly screen 120,000 compounds, which corresponds to about a third of those tested so far by various laboratories all over the world in the search for new parasite anti-transmission drugs. This result therefore paves the way to wider screens to identify even better compounds against parasite transmission. "

"The action of the identified chemotypes is to interrupt the life cycle of P. falciparum and therefore the spread of malaria to other individuals" comments Pietro Alano, researcher at ISS, adding that "the advantage of the new screening funnel is its efficiency and speed in identifying molecules active specifically against gametocytes as well as dual active molecules, that are able to kill the parasite stages

causing the disease symptoms. Today, elimination of malaria requires both types of drugs.”

In the past five years the global fight against malaria has come to a halt, exacerbated today by the effects of the Covid-19 pandemic on the health systems of the most affected countries, mainly in Africa. In 2021, 240 million new cases and 630,000 deaths, especially African children under the age of 5, was the price imposed by this parasite on the health of humanity, a scenario made increasingly worrying by the emergence of parasites and mosquitoes resistant to the available frontline drugs and insecticides.


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