2023-06-21 15:02:00
[헬스코리아뉴스 / 이충만] With the declaration of Corona 19 endemic, the number of overseas travelers is increasing, and malaria patients are increasing worldwide. It has been revealed that Korea is not a malaria-safe zone, as a recent malaria warning was issued. In response to this public health crisis, scientists have started to search for targets that can prevent malaria infection, and the mechanism of action of inhibiting a specific protein has emerged as a key to preventing malaria infection.
Nature published a study on the 12th (local time) that malaria infection can be prevented by inhibiting Plasmodium falciparum myosin A. The study was led by the National Center for Scientific Research in France.
The research team said, “More than 500,000 people die every year due to malaria. There are various antibiotics that can prevent and treat malaria, but Plasmodium Plasmodium (P. malaria) is showing drug resistance over time.”
In fact, the most problematic point in preventing and treating malaria worldwide is Plasmodium falciparum, and although the epidemic area is expanding, it is adding to the seriousness of the problem because it is not effective because it is resistant to existing antibiotics.
Malaria infectants have motility in complex human activities and mosquito life cycles. This is called gliding motility, and as a form of motility in a single cell unit, it is a form of movement that moves on a solid surface with power generated by consuming energy. Infectious worms reach host tissues and cells through this process.
The gliding motility of the infestation works through the glideosome protein. This protein is a macromolecular complex composed of adhesive proteins, and the core of this complex’s action is the interaction between actin (PfAct1), a major protein constituting muscle myofibrils, and myosin A, a motor protein that causes muscle contraction. This is called the class XIV myosin motor PfMyoA.
At this time, the research team pointed out the class XIV myosin motor PfMyoA, which is part of the glidosome, as a target for the therapeutic drug. The main idea is to prevent malaria infection by inhibiting PfMyoA.
The National Center for Scientific Research in France discovered ‘KNX-002’, a new small-molecule drug candidate, focusing on this mechanism. This drug was developed by selecting a substance that showed PfMyoA inhibitory activity among regarding 50,000 that existed in the compound repository.
Looking at the mechanism of action in contrast with the currently used malaria vaccine ‘RTS, S’, ‘KNX-002’ inhibits the glidosome’s PfMyoA protein to block the migration of infectious insects to the host. On the other hand, ‘RTS, S’ is a method of inhibiting cell infection by targeting proteins on the cell envelope of the infecting insect. Simply put, ‘KNX-002’ blocks migration for host infection, and ‘RTS, S’ prevents in vivo infection following host cell migration.
The research team conducted preclinical in vitro experiments to evaluate the preliminary efficacy of ‘KNX-002’. As a result, ‘KNX-002’ inhibited PfMyoA adenosine triphosphatase activity and effectively blocked asexual reproduction during the life cycle of Plasmodium.
The key is whether ‘KNX-002’ has a wide range of effects on the actual human body. ‘RTS, S’, the only licensed malaria vaccine, has a very low preventive efficacy of less than 50%, so much research is needed in the future.
The research team said, “The combination of ‘KNX-002’ and PfMyoA prevents the activation of efficient hydrolase and blocks gliding motility. It provided a clue to prevent it.”
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