Dihydroartemisinic acid is the biosynthetic precursor to artemisinin, the endoperoxide-containing natural product used to treat malaria. The conversion of dihydroartemisinic acid to artemisinin is a cascade reaction that involves C–C bond cleavage, hydroperoxide incorporation, and polycyclization to form the endoperoxide. Whether or not this reaction is enzymatically controlled has been controversial.
Recently, a promising technique has come forward in field of radiation-agriculture in which the natural polysaccharides are modified into useful oligomers after depolymerization. Ionizing radiation technology is a simple, pioneering, eco-friendly, and single step degradation process which is used in exploiting the efficiency of the natural polysaccharides as plant growth promoters. Arsenic (As) is a noxious and toxic to growth and development of medicinal plants. Artemisinin is obtained from the leaves of Artemisia annua L., which is effective in the treatment of malaria.
Management of uncomplicated malaria worldwide is threatened by the emergence in Asia of Plasmodium falciparum carrying variants of the pfk13 locus and exhibiting reduced susceptibility to artemisinin. Mutations in two other genes, ubp1 and ap2μ, are associated with artemisinin resistance in rodent malaria and with clinical failure of combination therapy in African malaria patients. Transgenic P. falciparum clones, each carrying orthologues of mutations in pfap2μ and pfubp1 associated with artemisinin resistance in Plasmodium chabaudi, were derived by Cas9 gene editing.
Endoperoxides (EPs) appear to be promising drug candidates against protozoal diseases, including malaria and leishmaniasis. Previous studies have shown that these drugs need an intracellular activation to exert their pharmacological potential. The efficiency of these drugs is linked to the extensive iron demand of these intracellular protozoal parasites.
These studies demonstrate the proof of concept of artemisinin therapeutic potential to improve survival in vitro of BMSCs exposed to ROS-induced apoptosis and suggest that artemisinin-mediated protection occurs via the activation of c-Raf-Erk1/2-p90rsk-CREB signaling pathway.
The pathogenic variant c.144T>G (p.N48K) in the clarin1 gene (CLRN1) results in progressive loss of vision and hearing in Usher syndrome IIIA (USH3A) patients.
Currently, the most effective antimalarial is artemisinin, which is extracted from the leaves of medicinal herb Artemisia annua L. (A. annua).
In 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency.
Apart from k13, pfarps10, pffd and pfmdr2 are also useful for molecular surveillance of artemisinin resistance especially where k13 mutation has not been reported.
Mass drug administration for malaria was well accepted by communities at high risk of malaria in Zanzibar, with high participation and completion rates.