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antimalarial drugs

Hydroxychloroquine Controversies: Clinical Trials, Epistemology, and the Democratization of Science

November 19, 2020 - 13:23 -- Open Access
Berlivet L, Löwy I
Med Anthropol Q. 2020 Nov 18

The claim that anti-malaria drugs, chloroquine and hydroxychloroquine, can cure COVID-19 became a focus of fierce political battles that pitted promoters of these pharmaceuticals, Presidents Bolsonaro and Trump among them, against "medical elites." At the center of these battles are different meanings of effectiveness in medicine, the complex role of randomized clinical trials (RCTs) in proving such effectiveness, the task of medical experts and the state in regulating pharmaceuticals, patients' activism, and the collective production of medical knowledge.

Inhibition of Plasmodium falciparum Lysyl-tRNA synthetase via an anaplastic lymphoma kinase inhibitor

November 19, 2020 - 13:15 -- Open Access
Zhou J, Huang Z, Zheng L, Hei Z, Wang Z, Yu B, Jiang L, Wang J, Fang P
Nucleic Acids Res. 2020 Nov 18;48(20):11566-11576

Aminoacyl-tRNA synthetases are attractive targets for the development of antibacterial, antifungal, antiparasitic agents and for the treatment of other human diseases. Lysyl-tRNA synthetase (LysRS) from this family has been validated as a promising target for the development of antimalarial drugs. Here, we developed a high-throughput compatible assay and screened 1215 bioactive compounds to identify Plasmodium falciparum cytoplasmic LysRS (PfLysRS) inhibitor.

Targeting the CD146/Galectin-9 axis protects the integrity of the blood-brain barrier in experimental cerebral malaria

November 19, 2020 - 13:08 -- Open Access
Duan H, Zhao S, Xiang J, Ju C, Chen X, Gramaglia I, Yan X
Cell Mol Immunol. 2020 Nov 17

Cerebral malaria (CM) is a life-threatening diffuse encephalopathy caused by Plasmodium falciparum, in which the destruction of the blood-brain barrier (BBB) is the main cause of death. However, increasing evidence has shown that antimalarial drugs, the current treatment for CM, do little to protect against CM-induced BBB damage. Therefore, a means to alleviate BBB dysfunction would be a promising adjuvant therapy for CM.

NOT Open Access | A proteomic glimpse into the effect of antimalarial drugs on Plasmodium falciparum proteome towards highlighting possible therapeutic targets

November 18, 2020 - 12:25 -- NOT Open Access
Dousti M, Manzano-Román R, Rashidi S, Barzegar G, Ahmadpour NB, Mohammadi A, Hatam G
Pathog Dis. 2020 Nov 17:ftaa071

There is no effective vaccine against malaria; therefore, chemotherapy is to date only choice to fight against this infectious disease. However, there are growing evidences of drug-resistance mechanisms in malaria treatments. Therefore, the identification of new drug targets is an urgent need for the clinic management of the disease. Proteomic approaches offer the chance of determining the effects of antimalarial drugs on the proteome of Plasmodium parasites.

Plasmodium berghei K13 Mutations Mediate In Vivo Artemisinin Resistance That Is Reversed by Proteasome Inhibition

November 11, 2020 - 14:33 -- Open Access
Simwela NV, Stokes BH, Aghabi D, Bogyo M, Fidock DA, Waters AP
mBio. 2020 Nov 10;11(6):e02312-20

The recent emergence of Plasmodium falciparum parasite resistance to the first line antimalarial drug artemisinin is of particular concern. Artemisinin resistance is primarily driven by mutations in the P. falciparum K13 protein, which enhance survival of early ring-stage parasites treated with the artemisinin active metabolite dihydroartemisinin in vitro and associate with delayed parasite clearance in vivo However, association of K13 mutations with in vivo artemisinin resistance has been problematic due to the absence of a tractable model.

An Update on Development of Small-Molecule Plasmodial Kinase Inhibitors

November 11, 2020 - 14:13 -- Open Access
Moolman C, Sluis RV, Beteck RM, Legoabe LJ
Molecules. 2020 Nov 7;25(21):E518

Malaria control relies heavily on the small number of existing antimalarial drugs. However, recurring antimalarial drug resistance necessitates the continual generation of new antimalarial drugs with novel modes of action. In order to shift the focus from only controlling this disease towards elimination and eradication, next-generation antimalarial agents need to address the gaps in the malaria drug arsenal.

NOT Open Access | Artemisinin-Ginkgo biloba extract combination therapy for Plasmodium yoelii

November 4, 2020 - 14:41 -- NOT Open Access
Zhang Q, Ao Z, Hu N, Hu X, Liao F, Han D
Parasitol Int. 2020 Oct 30:102226

Malaria remains a widespread life-threatening infectious disease, leading to an estimated 219 million cases and around 435,000 deaths. After an unprecedented success, the antimalarial progress is at a standstill. Therefore, new methods are urgently needed to decrease drug resistant and enhance antimalarial efficacy.

The impact of COVID-19 pandemic on malaria elimination

October 31, 2020 - 09:28 -- Open Access
Zawawi A, Alghanmi M, Alsaady I, Gattan H, Zakai H, Couper K
Parasite Epidemiol Control. 2020 Oct 20:e00187

SARS-CoV-2 has spread throughout the world and become the cause of the infectious coronavirus disease 2019 (COVID-19). As low- and middle-income countries shift increasingly to focus on identifying and treating COVID-19, questions are emerging about the impact this shift in focus will have on ongoing efforts to control other infectious diseases, such as malaria.

Molecular detection of drug resistant polymorphisms in Plasmodium falciparum isolates from Southwest, Nigeria

October 31, 2020 - 09:24 -- Open Access
Tola M, Ajibola O, Idowu ET, Omidiji O, Awolola ST, Amambua-Ngwa A.
BMC Res Notes. 2020 Oct 27;13(1):497

Nigeria bears 25% of global malaria burden despite concerted efforts towards its control and elimination. The emergence of drug resistance to first line drugs, artemisinin combination therapies (ACTs), indicates an urgent need for continuous molecular surveillance of drug resistance especially in high burden countries where drug interventions are heavily relied on. This study describes mutations in Plasmodium falciparum genes associated with drug resistance in malaria; Pfk13, Pfmdr1, PfATPase6 and Pfcrt in isolates obtained from 83 symptomatic malaria patients collected in August 2014, aged 1–61 years old from South-west Nigeria.

Artemisinin susceptibility in the malaria parasite Plasmodium falciparum: propellers, adaptor proteins and the need for cellular healing

October 28, 2020 - 09:23 -- Open Access
Sutherland CJ, Henrici RC, Artavanis-Tsakonas K
FEMS Microbiol Rev. 2020 Oct 23:fuaa056

Studies of the susceptibility of Plasmodium falciparum to the artemisinin family of antimalarial drugs provide a complex picture of partial resistance (tolerance) associated with increased parasite survival in vitro and in vivo. We present an overview of the genetic loci that, in mutant form, can independently elicit parasite tolerance. These encode kelch propeller domain protein PfK13, ubiquitin hydrolase UBP-1, actin filament-organising protein Coronin, also carrying a propeller domain, and the trafficking adaptor subunit AP-2μ.


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