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drug resistance

NOT Open Access | Computational prediction of the effects of non-synonymous single nucleotide polymorphisms on the GPI-anchor transamidase subunit GPI8p of Plasmodium falciparum

June 9, 2021 - 14:57 -- NOT Open Access
Singh SK, Reddy MS
Comput Biol Chem. 2021 Jun;92:107461

Drug resistance is increasingly evolving in malaria parasites; hence, it is important to discover and establish alternative drug targets. In this context, GPI-anchor transamidase (GPI-T) is a potential drug target primarily of its crucial role in the development and survival of the parasite in the GPI anchor biosynthesis pathway. The present investigation was undertaken to explore the plausible effects of nsSNP on the structure and functions of GPI-T subunit GPI8p of Plasmodium falciparum.

Parasite and Host Erythrocyte Kinomics of Plasmodium Infection

June 1, 2021 - 15:26 -- Open Access
Adderley J, Williamson T, Doerig C
Trends Parasitol. 2021 Jun;37(6):508-524

Malaria remains a heavy public health and socioeconomic burden in tropical and subtropical regions. Increasing resistance against front-line treatments implies that novel targets for antimalarial intervention are urgently required.

Assessing risks of Plasmodium falciparum resistance to select next-generation antimalarials

May 19, 2021 - 14:14 -- Open Access
Duffey M, Blasco B, Burrows JN, Wells TNC, Fidock DA, Leroy D
Trends Parasitol. 2021 May 14:S1471-4922(21)00086-6

Strategies to counteract or prevent emerging drug resistance are crucial for the design of next-generation antimalarials. In the past, resistant parasites were generally identified following treatment failures in patients, and compounds would have to be abandoned late in development. An early understanding of how candidate therapeutics lose efficacy as parasites evolve resistance is important to facilitate drug design and improve resistance detection and monitoring up to the postregistration phase.

NOT Open Access | Chemoproteomics for Plasmodium parasite drug target discovery

May 18, 2021 - 13:29 -- NOT Open Access
Lu KY, Mansfield C, Fitzgerald M, Derbyshire E
Chembiochem. 2021 May 17

Emerging Plasmodium parasite drug resistance is threatening progress towards malaria control and elimination. While recent efforts in cell-based high-throughput drug screening have produced first-in-class drugs with promising activities against different Plasmodium life cycle stages, most of these antimalarial agents have elusive mechanisms of action.

Molecular surveillance of drug resistance: Plasmodium falciparum artemisinin resistance single nucleotide polymorphisms in Kelch protein propeller (K13) domain from Southern Pakistan

April 14, 2021 - 07:48 -- Open Access
Najia Karim Ghanchi, Bushra Qurashi, Hadiqa Raees and Mohammad Asim Beg
Malaria Journal 2021 20:176, 7 April 2021

K13 propeller (k13) polymorphism are useful molecular markers for tracking the emergence and spread of artemisinin resistance in Plasmodium falciparum. Polymorphisms are reported from Cambodia with rapid invasion of the population and almost near fixation in south East Asia. The study describes single nucleotide polymorphisms in Kelch protein propeller domain of P. falciparum associated with artemisinin resistance from Southern Pakistan.

Historical trends and new surveillance of Plasmodium falciparum drug resistance markers in Angola

April 14, 2021 - 07:47 -- Open Access
Emily R. Ebel, Fátima Reis, Dmitri A. Petrov and Sandra Beleza
Malaria Journal 2021 20:175, 7 April 2021

Plasmodium falciparum resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) has historically posed a major threat to malaria control throughout the world. The country of Angola officially replaced CQ with artemisinin-based combination therapy (ACT) as a first-line treatment in 2006, but malaria cases and deaths have recently been rising. Many classic resistance mutations are relevant for the efficacy of currently available drugs, making it important to continue monitoring their frequency in Angola.

Drug resistance profile and clonality of Plasmodium falciparum parasites in Cape Verde: the 2017 malaria outbreak

April 7, 2021 - 12:43 -- Open Access
Silvania Da Veiga Leal, Daniel Ward, Fatima Nogueira, et al.
Malaria Journal 2021 20:172, 31 March 2021

Cape Verde is an archipelago located off the West African coast and is in a pre-elimination phase of malaria control. Since 2010, fewer than 20 Plasmodium falciparum malaria cases have been reported annually, except in 2017, when an outbreak in Praia before the rainy season led to 423 autochthonous cases. It is important to understand the genetic diversity of circulating P. falciparum to inform on drug resistance, potential transmission networks and sources of infection, including parasite importation.

NOT Open Access | Genomic and Genetic Approaches to Studying Antimalarial Drug Resistance and Plasmodium Biology

March 17, 2021 - 17:19 -- NOT Open Access
Okombo J, Kanai M, Deni I, Fidock DA
Trends Parasitol. 2021 Mar 11:S1471-4922(21)00035-0

Recent progress in genomics and molecular genetics has empowered novel approaches to study gene functions in disease-causing pathogens. In the human malaria parasite Plasmodium falciparum, the application of genome-based analyses, site-directed genome editing, and genetic systems that allow for temporal and quantitative regulation of gene and protein expression have been invaluable in defining the genetic basis of antimalarial resistance and elucidating candidate targets to accelerate drug discovery efforts.

Measurement of gene amplifications related to drug resistance in Plasmodium falciparum using droplet digital PCR

March 3, 2021 - 15:47 -- Open Access
Suttipat Srisutham, Kanokon Suwannasin, Rungniran Sugaram, Arjen M. Dondorp and Mallika Imwong
Malaria Journal 2021 20:120, 28 February 2021

Copy number variations (CNVs) of the Plasmodium falciparum multidrug resistance 1 (pfmdr1), P. falciparum plasmepsin2 (pfplasmepsin2) and P. falciparum GTP cyclohydrolase 1 (pfgch1) genes are associated with anti-malarial drug resistance in P. falciparum malaria. Droplet digital PCR (ddPCR) assays have been developed for accurate assessment of CNVs in several human genes. The aim of the present study was to develop and validate ddPCR assays for detection of the CNVs of P. falciparum genes associated with resistance to anti-malarial drugs.

NOT Open Access | Leveraging Peptaibol Biosynthetic Promiscuity for Next-Generation Antiplasmodial Therapeutics

February 11, 2021 - 09:29 -- NOT Open Access
Lee JW, Collins JE, Wendt KL, Chakrabarti D, Cichewicz RH
J Nat Prod. 2021 Feb 10

Malaria remains a worldwide threat, afflicting over 200 million people each year. The emergence of drug resistance against existing therapeutics threatens to destabilize global efforts aimed at controlling Plasmodium spp. parasites, which is expected to leave vast portions of humanity unprotected against the disease. To address this need, systematic testing of a fungal natural product extract library assembled through the University of Oklahoma Citizen Science Soil Collection Program has generated an initial set of bioactive extracts that exhibit potent antiplasmodial activity (EC50 < 0.30 μg/mL) and low levels of toxicity against human cells (less than 50% reduction in HepG2 growth at 25 μg/mL).


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