Research Highlights

doi:10.1038/nindia.2014.11 Published online 24 January 2014

Promising new anti-malarial

The broad spectrum anti-parasitic agent ivermectin inhibits the growth of malaria parasite Plasmodiumm falciparum, new research suggests, making it a promising anti-malarial candidate1 .

Ivermectin is already in use for treatment of diseases such as strongyloidiasis and onchocerciasis caused by nematodes. The researchers report that it also blocks the "nuclear-cytoplasmic shuttling of signal recognition particle (SRP) components" ultimately killing the malaria parasite P. falciparum. Ivermectin, an inhibitor of importin α and β at submicromolar concentration inhibited the nuclear import of PfSRP polypeptides, thereby killing the parasites, they report.

Researchers Renu Tuteja (left) and Pawan Malhotra

Protein targeting in the malaria parasite is a complex process and various sorting events that allow the proteins to get targeted to the right place are poorly understood in P. falciparum, says Renu Tuteja, one of the authors from the International Centre for Genetic Engineering& Biotechnology (ICGEB), New Delhi.

The team reported that the P. falciparum SRP is composed of six polypeptides — SRP9, SRP14, SRP19, SRP54, SRP68, SRP72 — and a 303 nt long SRP RNA. Co-localization studies using the four transgenic parasite lines expressing SRP-GFP chimeric proteins showed the nucleo-cytoplasmic localization for SRP9, SRP14, SRP19 and SRP54 proteins.

The researchers tested ivermectin's anti-malarial activity in vivo with infected mice. Ivermectin alone suppressed parasitemias compared to placebo-treated controls. All the mice administered with ivermectin survived up to 23 days, while the control mice died on day 13.

"These results suggest that ivermectin can be developed as an antimalarial in combination with other drugs," Tuteja adds.


References

  1. Panchal, M. et al. Plasmodium falciparum signal recognition particle components and anti-parasitic effect of ivermectin in blocking nucleo-cytoplasmic shuttling of SRP. Cell Death Dis. 5, e994 (2014) doi: 10.1038/cddis.2013.521 | Article | PubMed