Download or read book Drug Targets for Plasmodium Falciparum Historic to Future Perspectives written by Mohammed Tarique and published by Springer Nature. This book was released on with total page 205 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization and Analysis of Novel Antimalarial Drug Targets Plasmodium Falciparum Phosphatidylinositol Kinases written by Anna Rose Sternberg and published by . This book was released on 2020 with total page 372 pages. Available in PDF, EPUB and Kindle. Book excerpt: Artemisinin-based combination therapy (ACT) is the first-line treatment recommended for uncomplicated Plasmodium falciparum infections by the World Health Organization (WHO). ACTs are composed of an artemisinin (ART) drug and a longer lasting partner drug, typically with a mechanism of action (MOA) different from ARTs. With the exception of ARTs, there is widespread resistance to all antimalarial drug classes previously recommended for use against P. falciparum. However, the appearance of delayed clearance phenotype (DCP) infections due to reduced ACT efficacy in Southeast Asia [Noedl et al., 2008] threatens our ability to successfully treat multi-drug resistant P. falciparum malaria with ACTs. This also indicates the era of ARTs as leading antimalarial drugs may be reaching an end, so there is desperate need for the development of novel and potent antimalarials for use in next generation therapies.
Download or read book High throughput Prioritization of Putative Drug Targets in the Malaria Parasite Plasmodium Falciparum written by Misha Le Grange and published by . This book was released on 2015 with total page 202 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug resistance to almost all known antimalarials is widespread and is rapidly increasing. This resistance is due to the over and misuse of these antimalarials, thus new antimalarial drugs are necessary to help in the prevention and cure of this widespread disease. Continuous in-depth studies are being done on a handful of putative targets for future exploitation and use, but not many resources are available that focus on performing data mining and target identification on the complete malaria genome, together with relations to chemical compounds. The DISCOVERY Database is a web-based system, developed for the in silico selection of drug target proteins and lead compounds. It is a database filled with malaria information and aspects that might influence the druggability of a malaria parasite protein and guide a scientist in choosing the right ligand for a protein. DISCOVERY can aid in attempting to predict the interaction of ligands with proteins of interest, associating chemical compound with malaria proteins and selective chemical similarity searches. It can be used to mine information on malaria proteins, predict ligands and compare human and mosquito host characteristics. DISCOVERY2 was developed in Java with NetBeans. The protein sequences for the Plasmodium spp. included in DISCOVERY were downloaded from PlasmoDB; the Homo sapiens proteins were downloaded from Ensembl and the Anopheles gambiae proteins was downloaded from VectorBase. Even though DISCOVERY is primarily focused on Plasmodium falciparum it also contains information for all proteins from Plasmodium vivax, Plasmodium yoelii, Plasmodium knowlesi, Plasmodium chabaudi and Plasmodium berghei as well for the human vector and mosquito host. Protein information includes sequences and annotations, functional predictions, gene ontology terms, orthology information, structural information, metabolic pathways, predicted putative protein-ligand interactions, druggability predictions and literature links. Chemical compounds are also included. Recently approaches have illustrated the value of predicting the association of chemical compounds with putative drug targets, especially when the targets of compounds, like the Glaxo Smith Kline dataset with known activity against the parasite may be extrapolated, using protein-ligand interaction databases, like ChemProt. DISCOVERY attempts to use a similar approach in associating chemical compounds with malaria proteins, using sequence homology, and also selective chemical similarity searches. Chapter 1 of this dissertation is a literature review focusing on the in silico identification of potential drug targets. It also mentions a few techniques/approaches with which to accomplish this as well as target databases that can be used to help in the identification process. Chapter 2 describes the steps taken to run and score the Plasmodium falciparum proteins in a high throughput manner through DISCOVERY. Chapter 3 gives four case studies from DISCOVERY, a protein that had a low weighted score, a protein with a very high weighted score and two proteins with weighted scores in between the other two. And Chapter 4 concludes by looking at how researchers can use this study as a starting point. In this dissertation, DISCOVERY2 was used, in conjunction with Taverna pipelines, to study all Plasmodium falciparum proteins in a high throughput manner to be able to identify possible drug targets that might be of importance for future drug identification.
Download or read book Combating Antimalarial Drug Resistance written by Samuel Uzondu and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This chapter X-rayed antimalarial drug resistance (ADR) by plasmodium species with a particular focus on P. falciparum, which is the most deadly species of the malaria parasite responsible for over 90% of the global malaria burden domiciled in Sub-Saharan Africa. The introduction intently looked at malaria therapeutics across the decades and the development of drug resistance by the parasite. With the malaria parasite (P. falciparum) as the focal point, the mechanisms by which they develop resistance to antimalarial drugs was looked at, including factors affecting drug resistance development. Armed with this knowledge, the chapter also highlighted the therapeutic interventions taken against this hydra-headed monster together with their limitations and recent advances towards addressing those limitations or opening new frontiers for research exploration. Future perspectives that will provide research strategy and direction as possible tools for combating drug resistance development by the malaria parasite were also discussed.
Download or read book New Strategies for Drug Discovery and Development for Plasmodium Falciparum written by and published by . This book was released on 2000 with total page 33 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria continues as a major health threat throughout the tropical world and potential demand for antimalarials is higher than for any other medication yet the world faces a crisis-drug resistance is emerging and spreading faster than drugs are being developed and the flow in the pipeline of new drugs has all but stopped. This represents a particular threat to the US Military. In a short time there may be parts of the world where no effective antimalarial drug is available. The recent emergence of multidrug resistant malaria parasites has intensified this problem. Recognizing this emerging crisis, it is necessary to identify new strategies for the identification and development of new antimalarials. The goal of this work is the development of a framework for antimalarial drug development into the 21st century. A new strategy for drug development is urgently needed. Current drugs are based on a small number of target molecules or lead compounds and in most cases the target of drug action is yet to be identified. Resistance is emerging rapidly and the mechanisms of resistance are poorly understood. The identification of new targets or new candidate drugs based on an understanding of the parasite biology are key elements in this new strategy. Clearly the development of a new antimalarial will require both basic and applied research working in concert with one another. The goal of this work is to use a molecular genetic approach both in the identification of new drug targets and in the investigation of mechanisms of drug resistance. The research has focused on the two objectives, namely the analysis of critical genes in the Plasmodium falciparum for their role in drug resistance and as potential new drug targets, including the analysis of gene expression in response to drug treatment using the method of Serial Analysis of Gene Expression and the use of DNA Chip technology in the analysis of the yeast heterologous system.
Download or read book Plasmodium Falciparum Transporters as Antimalarial Drug Targets written by Anne-Catrin Uhlemann and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasmodiumfalciparum malaria poses one of the most important disease problems in the world. Despite decades of effort to improve disease outcome, the emergence and rapid dissemination of multi-drug resistant parasites has led to a disturbing increase in malaria mortality and morbidity. A critical limitation in managing multi-drug resistant falciparum malaria has been the incomplete understanding of both the underlying molecular mechanisms of drug resistance and the mode of action of widely used drugs. This study aimed to characterise the molecular mechanisms underlying multi- drug resistant malaria by studying the role of gene amplification in the P. falciparum multi-drug resistance gene 1 (pfmdrl) in determining parasite response to a variety of antimalarials in vitro and in vivo. In addition, P. falciparum ATPase 6 (PfATP6), a putative drug target of the widely used artemisinins, was also examined for possible drug-modulating mutations. First a real-time peR technique to measure amplification of pfmdri was developed and validated. This technique was used to determine pfmdri copy number in a unique set of field sample set (n = 600) collected in Northern Thailand, an area harbouring the world's most drug-resistant parasites. This allowed a comprehensive analysis of the importance of pfmdri amplification in (1) in vitro resistance to drugs, (2) in vivo response to mefloquine or mefloquine- artesunate therapy, (3) evolution of amplification in pre- and post-treatment samples. Subsequent studies also investigated the prevalence of pfmdrt amplification in Gabon, a Sub-Saharan country with very little mefloquine resistance. In addition, P. falciparum field isolates were studied for possible polymorphisms in PfATP6 and plasmid constructs generated to study the role of single nucleotide point mutations in the putative active site of the enzyme.
Download or read book Malaria written by Institute of Medicine and published by National Academies Press. This book was released on 1991-02-01 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is making a dramatic comeback in the world. The disease is the foremost health challenge in Africa south of the Sahara, and people traveling to malarious areas are at increased risk of malaria-related sickness and death. This book examines the prospects for bringing malaria under control, with specific recommendations for U.S. policy, directions for research and program funding, and appropriate roles for federal and international agencies and the medical and public health communities. The volume reports on the current status of malaria research, prevention, and control efforts worldwide. The authors present study results and commentary on the: Nature, clinical manifestations, diagnosis, and epidemiology of malaria. Biology of the malaria parasite and its vector. Prospects for developing malaria vaccines and improved treatments. Economic, social, and behavioral factors in malaria control.
Download or read book Nucleoside Drug Targets in Plasmodium Falciparum written by Huaqing Cui and published by . This book was released on 2010 with total page 191 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Global Technical Strategy for Malaria 2016 2030 written by World Health Organization and published by World Health Organization. This book was released on 2015-11-04 with total page 35 pages. Available in PDF, EPUB and Kindle. Book excerpt: The World Health Organization's Global Technical Strategy for Malaria 2016- 2030 has been developed with the aim to help countries to reduce the human suffering caused by the world's deadliest mosquito-borne disease. Adopted by the World Health Assembly in May 2015 it provides comprehensive technical guidance to countries and development partners for the next 15 years emphasizing the importance of scaling up malaria responses and moving towards elimination. It also highlights the urgent need to increase investments across all interventions - including preventive measures diagnostic testing treatment and disease surveillance- as well as in harnessing innovation and expanding research. By adopting this strategy WHO Member States have endorsed the bold vision of a world free of malaria and set the ambitious new target of reducing the global malaria burden by 90% by 2030. They also agreed to strengthen health systems address emerging multi-drug and insecticide resistance and intensify national cross-border and regional efforts to scale up malaria responses to protect everyone at risk.
Download or read book Plasmodium Falciparum Histone Deacetylases as Novel Antimalarial Drug Targets written by Thanh Nguyen Tran and published by . This book was released on 2010 with total page 278 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Current Topics in Malaria written by Alfonso J. Rodriguez-Morales and published by . This book was released on 2016-11-30 with total page 508 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Saving Lives Buying Time written by Institute of Medicine and published by National Academies Press. This book was released on 2004-09-09 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: For more than 50 years, low-cost antimalarial drugs silently saved millions of lives and cured billions of debilitating infections. Today, however, these drugs no longer work against the deadliest form of malaria that exists throughout the world. Malaria deaths in sub-Saharan Africaâ€"currently just over one million per yearâ€"are rising because of increased resistance to the old, inexpensive drugs. Although effective new drugs called "artemisinins" are available, they are unaffordable for the majority of the affected population, even at a cost of one dollar per course. Saving Lives, Buying Time: Economics of Malaria Drugs in an Age of Resistance examines the history of malaria treatments, provides an overview of the current drug crisis, and offers recommendations on maximizing access to and effectiveness of antimalarial drugs. The book finds that most people in endemic countries will not have access to currently effective combination treatments, which should include an artemisinin, without financing from the global community. Without funding for effective treatment, malaria mortality could double over the next 10 to 20 years and transmission will intensify.
Download or read book World Malaria Report 2019 written by World Health Organization and published by . This book was released on 2019-08-28 with total page 224 pages. Available in PDF, EPUB and Kindle. Book excerpt: The World Malaria Report 2019 provides a comprehensive update on global and regional malaria data and trends. The report tracks investments in malaria programs and research as well as progress across all intervention areas: prevention, diagnosis, treatment, elimination, and surveillance. It also includes dedicated chapters on the consequences of malaria on maternal infant and child health the "High Burden to High Impact" approach as well as biological threats to the fight against malaria. The 2019 report is based on information received from more than 80 countries and areas with ongoing malaria transmission. This information is supplemented by data from national household surveys and databases held by other organizations.
Download or read book An Overview of Tropical Diseases written by Amidou Samie and published by BoD – Books on Demand. This book was released on 2015-12-02 with total page 214 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tropical diseases affect millions of people throughout the world and particularly in the developing countries. The millennium development goals had specifically targeted HIV/AIDS and Malaria for substantial reduction as well as Tuberculosis while many other tropical diseases have been neglected. The new sustainable development goals have not made such distinction and have targeted all diseases for elimination for the improvement of the quality of life of human beings on earth. The present book was developed to provide an update on issues relevant to the treatment of selected tropical diseases such as tuberculosis, malaria, leishmaniasis, schistosomiasis and ectoparasites such as chiggers which are widely distributed throughout the world. The control of these infections has been hampered by the development of drug resistance and the lack of the development of new and more effective drugs. The understanding of the biochemical processes underlying drug activity is therefore essential for the potential elimination of these infections.
Download or read book Malaria Control and Elimination written by Frédéric Ariey and published by Methods in Molecular Biology. This book was released on 2020-07-17 with total page 341 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Molecular Advancements in Tropical Diseases Drug Discovery written by Gauri Misra and published by Academic Press. This book was released on 2020-05-12 with total page 156 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular Advancements in Tropical Diseases Drug Discovery presents in-depth knowledge relating to the detection of infection, epidemiology, drugs against various tropical diseases, new target sites for drug discovery and multidrug resistance issues using bioinformatics tools and approaches. The book's chapters are written by experts in their respective fields so that each disease is covered in a rational manner and with a solid foundation on existing facts and prospective research ideas. Updates knowledge about tropical diseases with recent advancements in the field Presents an overview of new research covering detection, infection, epidemiology and risk factors of the most common tropical diseases using bioinformatics tools Encompasses a detailed description of developments in drug discovery, new drugs and their molecular mechanisms of action
Download or read book Protein Kinases as Drug Targets written by Bert Klebl and published by John Wiley & Sons. This book was released on 2011-03-16 with total page 570 pages. Available in PDF, EPUB and Kindle. Book excerpt: This timely guide to kinase inhibitor drug development is the first to cover the entire drug pipeline, from target identification to compound development and clinical application. Edited by the pioneers in the field, on the drug development side this ready reference discusses classical medicinal chemistry approaches as well as current chemical genomics strategies. On the clinical side, both current and future therapeutic application areas for kinase inhibitor drugs are addressed, with a strong focus on oncology drugs. Backed by recent clinical experience with first-generation drugs in the battle against various forms of cancer, this is crucial reading for medicinal, pharmaceutical and biochemists, molecular biologists, and oncologists, as well as those working in the pharmaceutical industry.
