Anti-Malarial compound DDD107498 that inhibits protein synthesis discovered

Jun 18, 2015 10:27 IST

A novel anti-malarial compound DDD107498 that inhibits protein synthesis was discovered by the scientists. The study related to the discovery was published on 18 June 2015 in the Journal Nature.

The compound was found to have all the attributes of an anti-malarial drug which extends to multiple lifecycle stages of the Plasmodium parasite with good pharmacokinetic properties and an acceptable safety profile.

The results gain prominence as the malaria parasite has developed resistance to many of the anti-malarial drugs currently being used including the potent artemisinin.

Main findings related to compound DDD107498

  • It was found to target the translocation elongation factor 2 (eEF2) which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. This discovery of eEF2 as a viable anti-malarial drug target opens up new possibilities for drug discovery.
  • The excellent drug-like properties makes the compound fight the parasite even when administered as a single-dose treatment. For instance, in the case of mice infected with Plasmodium berghei, a single dose of the compound was found to reduce the parasitaemia by 90 per cent.
  • The compound was also found to have activity against both the sexual blood stages that cause the disease and the gametocytes that are responsible for malaria transmission.
  • It also exhibited chemoprotection through action on the liver stage.
  • It was found to have excellent activity against the P. falciparum parasite and against several other drug-resistant strains.
  • It fared far better than the currently used artesunate drug against both P. falciparum and P. vivax.
  • In the case of liver schizont stage, the compound was found to be effective even when the compound was introduced after infection with P. berghei liver stage was established. Liver schizont stage means the stage where malaria parasite in the sporozoite stage enters the bloodstream and goes straight into the liver where they infect the liver cells.
  • No signs of parasitaemia even after 30 days were found when the mice were treated with the compound prior to being infected with P. berghei sporozites, thus establishing its ability to prevent infection.

According to the paper, the compound has already progressed into advanced non-clinical development, with aim of entering into human clinical trials.

In 2013, there were 200 million cases of malaria, and nearly 0.6 million deaths across the world. In India, there were about 61 million malaria cases and nearly 116000 malaria deaths happened in 2013. This was despite the fact that number of malaria deaths per 100000 during the period 1990-2013 was reduced to half in India.

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