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Artemisinin resistance

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https://www.readbyqxmd.com/read/28726171/qsar-modeling-docking-and-admet-studies-for-exploration-of-potential-anti-malarial-compounds-against-plasmodium-falciparum
#1
Tabish Qidwai
Development of resistance in the Plasmodium falciparum to Artemisinin, the most effective anti-malarial compound, threatens malaria elimination tactics. To gain more efficacious Artemisinin derivatives, QSAR modeling and docking was performed. In the present study, 2D-QSAR model and molecular docking were used to evaluate the Artemisinin compounds and to reveal their binding modes and structural basis of inhibitory activity. Moreover, ADMET-related descriptors have been calculated to predict the pharmacokinetic properties of the effective compounds...
December 2016: In Silico Pharmacology
https://www.readbyqxmd.com/read/28724415/identification-and-characterization-of-the-antiplasmodial-activity-of-hsp90-inhibitors
#2
Claribel Murillo-Solano, Chunmin Dong, Cecilia G Sanchez, Juan C Pizarro
BACKGROUND: The recent reduction in mortality due to malaria is being threatened by the appearance of Plasmodium falciparum parasites that are resistant to artemisinin in Southeast Asia. To limit the impact of resistant parasites and their spread across the world, there is a need to validate anti-malarial drug targets and identify new leads that will serve as foundations for future drug development programmes targeting malaria. Towards that end, the antiplasmodial potential of several Hsp90 inhibitors was characterized...
July 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28724354/novel-plasmodium-falciparum-metabolic-network-reconstruction-identifies-shifts-associated-with-clinical-antimalarial-resistance
#3
Maureen A Carey, Jason A Papin, Jennifer L Guler
BACKGROUND: Malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including the frontline drug, artemisinin. Our limited understanding of Plasmodium biology hinders the elucidation of resistance mechanisms. In this regard, systems biology approaches can facilitate the integration of existing experimental knowledge and further understanding of these mechanisms. RESULTS: Here, we developed a novel genome-scale metabolic network reconstruction, iPfal17, of the asexual blood-stage P...
July 19, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28723328/artemisinin-resistant-plasmodium-falciparum-in-africa
#4
LETTER
Feng Lu, Richard Culleton, Jun Cao
No abstract text is available yet for this article.
July 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28723327/artemisinin-resistant-plasmodium-falciparum-in-africa
#5
LETTER
(no author information available yet)
New England Journal of Medicine, Volume 377, Issue 3, Page 305-306, July 2017.
July 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28719312/molecular-epidemiology-of-malaria-in-cameroon-and-c%C3%A3-te-d-ivoire-xxxi-kelch-13-propeller-sequences-in-plasmodium-falciparum-isolates-before-and-after-implementation-of-artemisinin-based-combination-therapy
#6
Joseph Allico Djaman, Dagnogo Olefongo, Aristide Berenger Ako, Jocelyne Roman, Vincent Foumane Ngane, Leonardo K Basco, Rachida Tahar
Artemisinin-resistant malaria has not been reported from Africa, but resistance can possibly spread from Asia or arise independently in Africa. The emergence of artemisinin resistance in Africa can be monitored by molecular assay of Kelch 13 (K13) propeller sequences. A total of 251 archived DNA samples of Plasmodium falciparum isolates collected in 2002, 2003, and 2006 in Yaounde, Cameroon, and 47 samples collected in 2006 and 2013 in Abidjan, Côte d'Ivoire, were analyzed for K13-propeller sequence polymorphism...
July 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28711439/updates-on-k13-mutant-alleles-for-artemisinin-resistance-in-plasmodium-falciparum
#7
REVIEW
Myo Thura Zaw, Nor Amalina Emran, Zaw Lin
BACKGROUND: In the fight against malaria caused by Plasmodium falciparum, the successes achieved by artemisinin were endangered by resistance of the parasites to the drug. Whole genome sequencing approach on artemisinin resistant parasite line discovered k13 gene associated with drug resistance. In vitro and in vivo studies indicated mutations in the k13 gene were linked to the artemisinin resistance. METHODOLOGY: The literatures published after April, 2015 up to December, 2016 on k13 mutant alleles for artemisinin resistance in Plasmodium falciparum and relevant literatures were comprehensively reviewed...
June 29, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28693890/artemisinin-and-chinese-medicine-as-tu-science
#8
Jia-Chen Fu
The story of discovery of artemisinin highlights the diversity of scientific values across time and space. Resituating artemisinin research within a broader temporal framework allows us to understand how Chinese drugs like qinghao came to articulate a space for scientific experimentation and innovation through its embodiment of alternating clusters of meanings associated with tu and yang within scientific discourse. Tu science, which was associated with terms like native, Chinese, local, rustic, mass, and crude, articulated a radical vision of science in the service of socialist revolutionary ideals...
July 7, 2017: Endeavour
https://www.readbyqxmd.com/read/28689867/ex-vivo-activity-of-proveblue-a-methylene-blue-against-field-isolates-of-plasmodium-falciparum-in-dakar-senegal-from-2013-2015
#9
Bécaye Fall, Marylin Madamet, Silman Diawara, Sébastien Briolant, Khalifa Ababacar Wade, Gora Lo, Aminata Nakoulima, Mansour Fall, Raymond Bercion, Mame Bou Kounta, Rémi Amalvict, Nicolas Benoit, Mamadou Wague Gueye, Bakary Diatta, Boubacar Wade, Bruno Pradines
Resistance to most antimalarial drugs has spread from Southeast Asia to Africa. Accordingly, new therapies to use with artemisinin-based combination therapy (triple ACT) are urgently needed. Proveblue, a methylene blue preparation, was found to exhibit antimalarial activity against Plasmodium falciparum strains in vitro. Proveblue has synergistic effects when used in combination with dihydroartemisinin, and has been shown to significantly reduce or prevent cerebral malaria in mice. The objectives of the current study were to evaluate the in vitro baseline susceptibility of clinical field isolates to Proveblue, compare its activity with that of other standard antimalarial drugs and define the patterns of cross-susceptibility between Proveblue and conventional antimalarial drugs...
July 6, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28688800/protein-degradation-systems-as-antimalarial-therapeutic-targets
#10
REVIEW
Caroline L Ng, David A Fidock, Matthew Bogyo
Artemisinin (ART)-based combination therapies are the most efficacious treatment of uncomplicated Plasmodium falciparum malaria. Alarmingly, P. falciparum strains have acquired resistance to ART across much of Southeast Asia. ART creates widespread protein and lipid damage inside intraerythrocytic parasites, necessitating macromolecule degradation. The proteasome is the main engine of Plasmodium protein degradation. Indeed, proteasome inhibition and ART have shown synergy in ART-resistant parasites. Moreover, ubiquitin modification is associated with altered parasite susceptibility to multiple antimalarials...
July 5, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/28687086/ivermectin-susceptibility-and-sporontocidal-effect-in-greater-mekong-subregion-anopheles
#11
Kevin C Kobylinski, Ratawan Ubalee, Alongkot Ponlawat, Chanyapat Nitatsukprasert, Siriporn Phasomkulsolsil, Thanaporn Wattanakul, Joel Tarning, Kesara Na-Bangchang, Patrick W McCardle, Silas A Davidson, Jason H Richardson
BACKGROUND: Novel vector control methods that can directly target outdoor malaria transmission are urgently needed in the Greater Mekong Subregion (GMS) to accelerate malaria elimination and artemisinin resistance containment efforts. Ivermectin mass drug administration (MDA) to humans has been shown to effectively kill wild Anopheles and suppress malaria transmission in West Africa. Preliminary laboratory investigations were performed to determine ivermectin susceptibility and sporontocidal effect in GMS Anopheles malaria vectors coupled with pharmacokinetic models of ivermectin at escalating doses...
July 7, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28668681/targeting-the-active-sites-of-malarial-proteases-for-antimalarial-drug-discovery-approaches-progress-and-challenges
#12
REVIEW
Kuldeep K Roy
Malaria is an infectious disease causing huge mortality and morbidity worldwide. Although antimalarial drugs are effective in several parts of the world, there is a serious threat to malaria control that malaria parasites are continuously developing widespread resistance against currently available antimalarial drugs, including artemisinin. Such widespread antimalarial drug resistance certifies the need of improving the efficacy of existing or new drugs, and developing alternative treatments through the identification of novel drug targets and development of candidate drugs...
June 28, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28667301/knockout-of-the-peroxiredoxin-5-homologue-pfaop-does-not-affect-the-artemisinin-susceptibility-of-plasmodium-falciparum
#13
Carine F Djuika, Verena Staudacher, Cecilia P Sanchez, Michael Lanzer, Marcel Deponte
Artemisinins are the current mainstay of malaria chemotherapy. Their exact mode of action is an ongoing matter of debate, and several factors have recently been reported to affect an early stage of artemisinin resistance of the most important human malaria parasite Plasmodium falciparum. Here, we identified a locus on chromosome 7 that affects the artemisinin susceptibility of P. falciparum in a quantitative trait locus analysis of a genetic cross between strains 7G8 and GB4. This locus includes the peroxiredoxin gene PFAOP...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28664674/adaptive-immunity-is-essential-in-preventing-recrudescence-of-plasmodium-yoelii-malaria-parasites-after-artesunate-treatment
#14
Carla Claser, Zi Wei Chang, Bruce Russell, Laurent Renia
Artemisinin based antimalarials, such as artesunate (ART), alone or in combination, are the mainstay of the therapy against malaria caused by Plasmodium falciparum. However the emergence and spread of artemisinin resistance threatens the future success of its global malaria eradication. While much of the reported artemisinin resistance can be attributed to mutations intrinsic to the parasite, a significant proportion of treatment failures are thought to be due to other factors such as the host's immune system...
June 30, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28646896/detection-of-the-plasmodium-falciparum-kelch-13-gene-p553l-mutation-in-sporozoites-isolated-from-mosquito-salivary-glands-in-south-central-vietnam
#15
Yoshimasa Maeno, Nguyen Tuyen Quang, Richard Culleton, Satoru Kawai, Gaku Masuda, Kaoru Hori, Shusuke Nakazawa, Ron P Marchand
BACKGROUND: Plasmodium falciparum has developed resistance against artemisinin in Southeast Asia. Mutations in the P. falciparum Kelch-13 (Pfk13) gene are associated with artemisinin resistance in vitro and in vivo. We investigated the prevalence of mutations in PfK13 from sporozoite-stage parasites isolated from the salivary glands of Anopheles dirus mosquitoes. METHODS: Mosquitoes were caught by human-landing catches at two locations within the Khanh Phu commune, South-Central Vietnam...
June 24, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28637430/malaria-control-by-commodities-without-practical-malariology
#16
J Kevin Baird
Malaria remains a serious clinical and public health problem, the object of an ongoing technological and humanitarian struggle to abate the very substantial harm done. The manner by which humanity approached malaria control changed abruptly and profoundly after 1945 with the advent of the insecticide DDT. Malariologists in the first half of the twentieth century conceived precise modifications to natural or man-made environments aimed at making those less hospitable to specific anopheline mosquito vector species...
June 21, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28635296/benzoxaborole-antimalarial-agents-part-5-lead-optimization-of-novel-amide-pyrazinyloxy-benzoxaboroles-and-identification-of-a-preclinical-candidate
#17
Yong-Kang Zhang, Jacob J Plattner, Eric E Easom, Robert T Jacobs, Denghui Guo, Yvonne R Freund, Pamela Berry, Vic Ciaravino, John C L Erve, Philip J Rosenthal, Brice Campo, Francisco-Javier Gamo, Laura M Sanz, Jianxin Cao
Carboxamide pyrazinyloxy benzoxaboroles were investigated with the goal to identify a molecule with satisfactory antimalarial activity, physicochemical properties, pharmacokinetic profile, in vivo efficacy, and safety profile. This optimization effort discovered 46, which met our target candidate profile. Compound 46 had excellent activity against cultured Plasmodium falciparum, and in vivo against P. falciparum and P. berghei in infected mice. It exhibited good PK properties in mice, rats, and dogs. It was highly active against the other 11 P...
June 29, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28634831/malaria-2017-update-on-the-clinical-literature-and-management
#18
REVIEW
Johanna P Daily
PURPOSE OF REVIEW: Malaria is a prevalent disease in travelers to and residents of malaria-endemic regions. Health care workers in both endemic and non-endemic settings should be familiar with the latest evidence for the diagnosis, management and prevention of malaria. This article will discuss the recent malaria epidemiologic and medical literature to review the progress, challenges, and optimal management of malaria. RECENT FINDINGS: There has been a marked decrease in malaria-related global morbidity and mortality secondary to malaria control programs over the last few decades...
June 20, 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28620813/an-in-silico-insight-into-the-substrate-binding-characteristics-of-the-active-site-of-amorpha-4-11-diene-synthase-a-key-enzyme-in-artemisinin-biosynthesis
#19
Habib Eslami, Seyed Kaveh Mohtashami, Maryam Taghavi Basmanj, Maryam Rahati, Hamzeh Rahimi
The enzyme amorphadiene synthase (ADS) conducts the first committed step in the biosynthetic conversion of the substrate farnesyl pyrophosphate (FPP) to artemisinin, which is a highly effective natural product against multidrug-resistant strains of malaria. Due to the either low abundance or low turn-over rate of the enzyme, obtaining artemisinin from both natural and synthetic sources is costly and laborious. In this in silico study, we strived to elucidate the substrate binding site specificities of the ADS, with the rational that unraveling enzyme features paves the way for enzyme engineering to increase synthesis rate...
July 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28615016/ex-vivo-susceptibility-and-genotyping-of-plasmodium-falciparum-isolates-from-pikine-senegal
#20
Aminata Mbaye, Amy Gaye, Baba Dieye, Yaye D Ndiaye, Amy K Bei, Muna Affara, Awa B Deme, Mamadou S Yade, Khadim Diongue, Ibrahima M Ndiaye, Tolla Ndiaye, Mouhamed Sy, Ngayo Sy, Ousmane Koita, Donald J Krogstad, Sarah Volkman, Davis Nwakanma, Daouda Ndiaye
BACKGROUND: The monitoring of Plasmodium falciparum sensitivity to anti-malarial drugs is a necessity for effective case management of malaria. This species is characterized by a strong resistance to anti-malarial drugs. In Senegal, the first cases of chloroquine resistance were reported in the Dakar region in 1988 with nearly 7% population prevalence, reaching 47% by 1990. It is in this context that sulfadoxine-pyrimethamine temporarily replaced chloroquine as first line treatment in 2003, pending the introduction of artemisinin-based combination therapy in 2006...
June 14, 2017: Malaria Journal
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