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antimalarial drug

A Prioritized and Validated Resource of Mitochondrial Proteins in Plasmodium Identifies Unique Biology

September 14, 2021 - 09:32 -- Open Access
van Esveld SL, Meerstein-Kessel L, Huynen MA, et al.
mSphere. 2021 Sep 8:e0061421

Plasmodium species have a single mitochondrion that is essential for their survival and has been successfully targeted by antimalarial drugs. Most mitochondrial proteins are imported into this organelle, and our picture of the Plasmodium mitochondrial proteome remains incomplete. Many data sources contain information about mitochondrial localization, including proteome and gene expression profiles, orthology to mitochondrial proteins from other species, coevolutionary relationships, and amino acid sequences, each with different coverage and reliability.

Antimalarial drug resistance in the Central and Adamawa regions of Cameroon: Prevalence of mutations in P. falciparum crt, Pfmdr1, Pfdhfr and Pfdhps genes

August 25, 2021 - 16:18 -- Open Access
Tuedom AGB, Sarah-Matio EM, Nsango SE, et al.
PLoS One. 2021 Aug 19;16(8):e0256343

The spread of Plasmodium falciparum resistant parasites remains one of the major challenges for malaria control and elimination in Sub Saharan Africa. Monitoring of molecular markers conferring resistance to different antimalarials is important to track the spread of resistant parasites and to optimize the therapeutic lifespan of current drugs. This study aimed to evaluate the prevalence of known mutations in the drug resistance genes Pfcrt, Pfmdr1, Pfdhfr and Pfdhps in two different epidemiological settings in Cameroon. Dried blood spots collected in 2018 and 2019 from asymptomatic individuals were used for DNA extraction and then the Plasmodium infection status was determined byPCR.

NOT Open Access | Associations between varied susceptibilities of PfATP4 inhibitors and genotypes in Ugandan Plasmodium falciparum isolates

August 4, 2021 - 15:56 -- NOT Open Access
Kreutzfeld O, Rasmussen SA, Rosenthal PJ, et al.
Antimicrob Agents Chemother. 2021 Aug 2:AAC0077121

Among novel compounds under recent investigation as potential new antimalarial drugs are three independently developed inhibitors of the Plasmodium falciparum P-type ATPase (PfATP4): KAE609 (cipargamin), PA92, and SJ733. We assessed ex vivo susceptibilities to these compounds of 374 fresh P. falciparum isolates collected in Tororo and Busia districts, Uganda from 2016-2019. Median IC50s were 65 nM for SJ733, 9.1 nM for PA92, and 0.5 nM for KAE609. Sequencing of pfatp4 for 218 of these isolates demonstrated many non-synonymous single nucleotide polymorphisms; the most frequent mutations were G1128R (69% of isolates mixed or mutant), Q1081K/R (68%), G223S (25%), N1045K (16%) and D1116G/N/Y (16%).

An SR protein is essential for activating DNA repair in malaria parasites

July 28, 2021 - 13:49 -- Open Access
Goyal M, Singh BK, Simantov K, Kaufman Y, Eshar S, Ron D
J Cell Sci. 2021 Jul 22:jcs.258572

Plasmodium falciparum, the parasite responsible for the deadliest form of human malaria, replicates within the erythrocytes of its host where it encounters numerous pressures that cause extensive DNA damage, which must be repaired efficiently to ensure parasite survival. Malaria parasites, which lost the NHEJ pathway for repairing DNA double strand breaks, have evolved unique mechanisms that enable them to robustly maintain genome integrity under such harsh conditions. However, the nature of these adaptations is unknown.

Intermittent preventive treatment for malaria in infants

July 21, 2021 - 17:07 -- Open Access
Esu EB, Oringanje C, Meremikwu MM
Cochrane Database Syst Rev. 2021 Jul 17;7:CD011525

Intermittent preventive treatment could help prevent malaria in infants (IPTi) living in areas of moderate to high malaria transmission in sub-Saharan Africa. The World Health Organization (WHO) policy recommended IPTi in 2010, but its adoption in countries has been limited.

Antimalarial drugs-are they beneficial in rheumatic and viral diseases?-considerations in COVID-19 pandemic

July 6, 2021 - 14:27 -- Open Access
Grygiel-Górniak B
Clin Rheumatol. 2021 Jul 3

The majority of the medical fraternity is continuously involved in finding new therapeutic schemes, including antimalarial medications (AMDs), which can be useful in combating the 2019-nCoV: coronavirus disease (COVID-19). For many decades, AMDs have been widely used in the treatment of malaria and various other anti-inflammatory diseases, particularly to treat autoimmune disorders of the connective tissue.

NOT Open Access | Host-targeted Interventions as an Exciting Opportunity to Combat Malaria

July 6, 2021 - 14:12 -- NOT Open Access
Vijayan K, Wei L, Glennon EKK, Mattocks C, Bourgeois N, Staker B, Kaushansky A
Chem Rev. 2021 Jul 1

Terminal and benign diseases alike in adults, children, pregnant women, and others are successfully treated by pharmacological inhibitors that target human enzymes. Despite extensive global efforts to fight malaria, the disease continues to be a massive worldwide health burden, and new interventional strategies are needed. Current drugs and vector control strategies have contributed to the reduction in malaria deaths over the past 10 years, but progress toward eradication has waned in recent years.

NOT Open Access | Transgenic pyrimethamine-resistant plasmodium falciparum reveals transmission-blocking potency of P218, a novel antifolate candidate drug

July 6, 2021 - 13:04 -- NOT Open Access
Posayapisit N, Pengon J, Prommana P, Shoram M, Yuthavong Y, Uthaipibull C, Kamchonwongpaisan S, Jupatanakul N
Int J Parasitol. 2021 Jul;51(8):635-642

Antimalarial drugs capable of targeting multiple parasite stages, particularly the transmissible stages, can be valuable tools for advancing the malaria elimination agenda. Current antifolate drugs such as pyrimethamine can inhibit replicative parasite stages in both humans and mosquitoes, but antifolate resistance remains a challenge. The lack of reliable gametocyte-producing, antifolate-resistant Plasmodium falciparum laboratory strain hinders the study of new antifolate compounds that can overcome antifolate resistance including development stages in the mosquito.

NOT Open Access | Structural analyses of the malaria parasite aminoacyl-tRNA synthetases provide new avenues for antimalarial drug discovery

June 30, 2021 - 11:28 -- NOT Open Access
Chhibber-Goel J, Yogavel M, Sharma A
Protein Sci. 2021 Jun 28

Malaria is a parasitic illness caused by the genus Plasmodium from the apicomplexan phylum. Five plasmodial species of P. falciparum, P. knowlesi, P. malariae, P. ovale and P. vivax are responsible for causing malaria in humans. According to the World Malaria Report 2019, there were 229 million cases and ~ 0.04 million deaths of which 67% were in children below five years of age.

NOT Open Access | Bold measures to accelerate malaria elimination

June 22, 2021 - 14:07 -- NOT Open Access
Price RN
Lancet Infect Dis. 2021 Jun 17:S1473-3099(21)00003-7

In the Greater Mekong subregion, intense drug pressure and indiscriminate use of poor-quality antimalarial drugs has led to the emergence of antimalarial resistance to all widely used drugs, including the artemisinin derivatives.


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