A new study has used robotic screening for shortlisting chemical compounds
which could be ‘prevent’ malaria
According to WHO, there were 219 million cases of malaria worldwide and approximately 435,000 deaths in 2017. Malaria is an infectious disease caused by parasites Plasmodium falciparum or Plasmodium vivax. These parasites start their lifecycle when an infected mosquito transmits sporozoites into a human when it feeds on human blood. Some of these sporozoites cause an infection inside the human liver as they replicate. Subsequently, parasite bursts into red blood cells to start the infection. When blood gets infected, symptoms of malaria like chills, fever etc. appear in a person.
Currently available drugs for malaria generally appease symptoms of the disease ‘after’ the infection had occurred. They block replication of parasites in the human blood, however they cannot prevent transmission to new people via mosquitoes because the infection has already taken place. When an infected person gets bitten by a mosquito, the mosquito carries the infection to another person continuing the vicious cycle of infection. Unfortunately, malaria parasites are becoming resistant to most commercially available anti-malarial drugs. There is an urgent need for new antimalarials which could not just treat symptoms but also prevent malaria infection from reaching the bloodstream so that it cannot be transferred to other people.
Targeting a new stage in parasite’s lifecycle
In a new study published in Science, researchers have targeted the malaria parasite at its lifecycle’s earlier stage – i.e. when the parasite first starts to infect the human liver. This is prior to the stage where the parasite starts replicating in the blood and causes infection to the person. Researchers took two years to extract malaria parasites from inside of thousands of mosquitos using modern technology of robotics. For their study, they used Plasmodium berghei, a relative parasite which infects only mice. First, the mosquitoes were infected by the parasite, then sporozoites were extracted from these infected mosquitos – some of them were dried, frozen so not of any use. These sporozoites were then taken to the drug screening facility where potential drugs/inhibitors/chemical compounds were tested for their effect. In one round about 20,000 compounds could be tested by using a robotic technology and sound waves wherein minute amounts of each chemical compound were added i.e. one compound added per every sporozoite cell. Each compound’s capability to kill the parasite or even block its replication was evaluated. The compounds which were toxic to liver cells were eliminated from the list. Testing was done for the same set of compounds on other Plasmodium species as well and also on other lifecycle stages apart from liver stage.
Chemical leads identified
A total of more than 500,000 chemical compounds were tested for their capability to stop the parasite when it’s at the human liver stage. After many rounds of testing, 631 compounds were shortlisted which were seen to block malaria infection before symptoms began so potentially preventing transmission into blood, new mosquitoes and new people. 58 among these 631 compounds even blocked the parasite’s energy-generating process in the mitochondria
This study could be the foundation for developing next generation novel ‘malaria prevention’ drugs. The research has been carried out in the open-source community which allows other research groups around the globe to freely use this information to further their work. Researchers want to test the 631 promising drug candidates to analyse their effectiveness and these compounds will also need to be checked for their safety for human consumption. Malaria urgently needs a novel drug which is affordable and can be delivered to any part of the world without additional demands of infrastructure, healthcare personnel or other resources.
Yevgeniya Antonova-Koch 2018, ‘Open-source discovery of chemical leads for next-generation chemoprotective antimalarials’, Science, Vol. 362, no.6419, DOI: https://doi.org/10.1126/science.aat9446