Study on the antimalarial mechanism of artemisinin by acting on host red blood cell membrane based on chemical proteomics technology

Malaria is a life-threatening disease caused by the protozoan parasite Plasmodium in the world. Artemisinin-based combination therapies (ACTs) has been adopted as a first-line treatment for uncomplicated Plasmodium falciparum malaria by World Health Organization (WHO). However, resistance to artemisinins and partner drugs is now causing the failure of P. falciparum ACTs in southeast Asia. Therefore, it is critical to understand artemisinin’s mechanism of action in order to find an effective method to conquer the resistance of malaria parasites in clinical or to design artemisinin derivatives with better antimalarial activity. Previous work confirmed that the total protein expression of Plasmodium falciparum 3D7-infected red blood cell (IRBC) membrane was down-regulated after 4 h treatment using 500 nM dihydroartemisinin. The hypothesis was that artemisinin exerts antimalarial effects by directly acting on the plasma membrane of IRBC.  Using pull-downs followed by immunoblotting to validate some selected artemisinin targets and also using heterologous expression system to validate the targets’interaction with AP1 in vitro, selecting a specific protein for artemisinin’s action. Finally, attempt is to further explore the function of the target protein in the anti-malarial process of artemisinin by using several gene manipulation methods related to gene silencing and overexpression, to reveal the antimalarial mechanism of artemisinin. This study will provide a critical guideline for artemisinin resistance control in malaria parasites and lay the foundation for developing new artemisinin-based antimalarial drugs.

Project details

Basic Science
Drug Resistance
Drug-based Strategies

Jan 2019 — Dec 2021

$31,116

China