Novel antimalarial compound may help avoid drug resistance
doi:10.1038/nindia.2021.104 Published online 22 July 2021
A novel antimalarial compound has shown promise in rapidly wiping out malaria parasites in infected mice with a single dose, while largely avoiding the development of treatment resistance1.
This finding, by an international research team, suggests that the new compound could be a step towards a single, low-dose cure for malaria infections.
Plasmodium falciparum, the malaria parasite that triggers malignant malaria, has developed resistance to first-line artemisinin-based combination therapies. Such resistance continues to rise in South-east Asia and is also a threat to people in malaria-endemic regions of Africa.
To find a way around this, the scientists, including a researcher from the Syngene International Limited in Bangalore, India, screened 800 compounds from drug-discovery programmes for molecules that target one of 33 human proteins that have analogues in malaria parasites.
One of these compounds, named MMV688533, showed promising drug properties and killed malaria parasites in culture and in infected mice with a single oral dose. The compound was effective against the parasites only when they were growing inside the host’s red blood cells.
The compound was as potent as existing antimalarial drugs such as chloroquine and piperaquine. It didn’t affect blood pressure and exert toxic effects on the heart in guinea pigs, suggesting that it is safe.
The researchers found that the P. falciparum parasites developed only minimal resistance when repeatedly exposed to escalating doses of the compound. They say that the compound could be effective in humans with relatively low single doses, offering a low-cost treatment for malaria.
1. Murithi, J. M. et al. The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to Plasmodium falciparum parasite resistance. Sci. Transl. Med. 13, eabg6013 (2021)