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NOT Open Access | Molecular Mechanisms of Drug Resistance in Plasmodium falciparum Malaria

September 10, 2020 - 14:25 -- NOT Open Access
Wicht KJ, Mok S, Fidock DA
Annu Rev Microbiol. 2020 Sep 8;74:431-454

Understanding and controlling the spread of antimalarial resistance, particularly to artemisinin and its partner drugs, is a top priority. Plasmodium falciparum parasites resistant to chloroquine, amodiaquine, or piperaquine harbor mutations in the P. falciparum chloroquine resistance transporter (PfCRT), a transporter resident on the digestive vacuole membrane that in its variant forms can transport these weak-base 4-aminoquinoline drugs out of this acidic organelle, thus preventing these drugs from binding heme and inhibiting its detoxification.

Global research on artemisinin and its derivatives: Perspectives from patents

September 5, 2020 - 15:40 -- Open Access
Liu K, Zuo H, Li G, Yu H, Hu Y
Pharmacol Res. 2020 Sep;159:105048

The isolation of artemisinin in 1971 heralded the beginning of a new era in antimalarial drug therapy, and artemisinin-based combination therapies are currently the mainstay of malaria treatment worldwide. Artemisinin-related studies have been extensively and intensively executed in the last few decades. However, although many purely technological reviews have been completed in this field, studies on artemisinin from the perspective of patents are still very limited. In terms of the importance of patents for academic research and commercial development, this study aims to reveal the overall patent landscape of artemisinin in the temporal, spatial, and technological dimensions. This work may provide a useful reference for relevant decision-making by researchers, investors, and policymakers.

NOT Open Access | A combined Raman optical activity and vibrational circular dichroism study on artemisinin-type products

August 10, 2020 - 14:34 -- NOT Open Access
Bogaerts J, Desmet F, Aerts R, Bultinck P, Herrebout W, Johannessen C
Phys Chem Chem Phys. 2020 Aug 5

Artemisinin and two of its derivatives, dihydroartemisinin and artesunate, which are front line drugs against malaria, were investigated using Raman optical activity (ROA) and vibrational circular dichroism (VCD) experiments, both supported by density functional theory (DFT) level calculations. The experimental techniques combined with DFT calculations could show that dihydroartemisinin was present as an epimeric mixture in solution.

K13-Mediated Reduced Susceptibility to Artemisinin in Plasmodium falciparum Is Overlaid on a Trait of Enhanced DNA Damage Repair

August 10, 2020 - 14:32 -- Open Access
Xiong A, Prakash P, Gao X, Chew M, Tay IJJ, Woodrow CJ, Engelward BP, Han J, Preiser PR
Cell Rep. 2020 Aug 4;32(5):107996

Southeast Asia has been the hotbed for the development of drug-resistant malaria parasites, including those with resistance to artemisinin combination therapy. While mutations in the kelch propeller domain (K13 mutations) are associated with artemisinin resistance, a range of evidence suggests that other factors are critical for the establishment and subsequent transmission of resistance in the field.

Safety of Artemisinin Derivatives in the First Trimester of Pregnancy: A Controversial Story

August 5, 2020 - 16:21 -- Open Access
D'Alessandro S, Menegola E, Parapini S, Taramelli D, Basilico N
Molecules. 2020 Jul 31;25(15):E3505

Artemisinin combination therapy (ACT) is recommended by the World Health Organization (WHO) as first line treatment for uncomplicated malaria both in adults and children. During pregnancy, ACT is considered safe only in the second and third trimester, since animal studies have demonstrated that artemisinin derivatives can cause foetal death and congenital malformation within a narrow time window in early embryogenesis.

Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda

August 5, 2020 - 15:14 -- Open Access
Uwimana A, Legrand E, Stokes BH, Ndikumana JM, Warsame M, Umulisa N, Ngamije D, Munyaneza T, Mazarati JB, Munguti K, Campagne P, Criscuolo A, Ariey F, Murindahabi M, Ringwald P, Fidock DA, Mbituyumuremyi A, Menard D
Nat Med. 2020 Aug 3. doi: 10.1038/s41591-020-1005-2

Artemisinin resistance (delayed P. falciparum clearance following artemisinin-based combination therapy), is widespread across Southeast Asia but to date has not been reported in Africa. Here we genotyped the P. falciparum K13 (Pfkelch13) propeller domain, mutations in which can mediate artemisinin resistance, in pretreatment samples collected from recent dihydroarteminisin-piperaquine and artemether-lumefantrine efficacy trials in Rwanda.

Efficacy and tolerability of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: a systematic review and individual patient data meta-analysis

August 3, 2020 - 16:31 -- Open Access
Saito M, Mansoor R, Kennon K, Guérin PJ, et al.
Lancet Infect Dis. 2020 Aug;20(8):943-952

Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum malaria in pregnant women is scarce and assessed in varied ways. We did a systematic literature review and individual patient data (IPD) meta-analysis to compare the efficacy and tolerability of different artemisinin-based or quinine-based treatments for malaria in pregnant women.

Plasmodium falciparum ATP4 inhibitors to treat malaria: worthy successors to artemisinin

August 3, 2020 - 15:51 -- Open Access
Ashley EA, Phyo AP
Lancet Infect Dis. 2020 Aug; (8):883-885

Progress in controlling malaria has slowed in recent years and the annual death toll remains above 400 000 globally, with most deaths caused by Plasmodium falciparum.

NOT Open Access | Artemisinin suppresses myocardial ischemia-reperfusion injury via NLRP3 inflammasome mechanism

August 3, 2020 - 12:26 -- NOT Open Access
Wang F, Gao Q, Yang J, Wang C, Cao J, Sun J, Fan Z, Fu L
Mol Cell Biochem. 2020 Jul 29

Artemisinin is known for its pharmaceutical effect against malaria and received increased attention for its other potential function. Mounting evidence suggest that artemisinin could also exert cardioprotective effects while the understanding of its regulatory mechanism is still limited. This study is designed to investigate the role of artemisinin in myocardial ischemia/reperfusion (I/R) injury and the involvement of NLRP3 inflammasome. Artemisinin was administrated for 14 consecutive days intragastrically before I/R injury. Cardiac function was assessed by echocardiography. Infarct area was observed through HE and TTC staining.

Transcriptome analyses revealed the ultraviolet B irradiation and phytohormone gibberellins coordinately promoted the accumulation of artemisinin in Artemisia annua L

July 13, 2020 - 15:43 -- Open Access
Ma T, Gao H, Zhang D, Shi Y, Zhang T, Shen X, Wu L, Xiang L, Chen S
Chin Med. 2020 Jul 1;15:67

Artemisinin-based combination therapy has become the preferred approach for treating malaria and has successfully reduced malaria-related mortality. Currently, the main source of artemisinin is Artemisia annua L., and thus, it is of strategic importance to enhance artemisinin contents in A. annua plants. Phytohormones and illumination are known to be important external environmental factor that can have notable effects on the production of secondary metabolite. The activities of different hormones can be influenced to varying degrees by light, and thus light and hormones may jointly regulate various processes in plants. Here, we performed transcriptome and metabolome analyses revealed that ultraviolet B irradiation and phytohormone gibberellins coordinately promoted the accumulation of artemisinin in Artemisia annua.


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