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Plasmodium falciparum

  • Atypical Molecular Basis for Drug Resistance to Mitochondrial Function Inhibitors in <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span>
    Mechanisms of Resistance
    Atypical Molecular Basis for Drug Resistance to Mitochondrial Function Inhibitors in Plasmodium falciparum

    The continued emergence of drug-resistant Plasmodium falciparum parasites hinders global attempts to eradicate malaria, emphasizing the need to identify new antimalarial drugs. Attractive targets for chemotherapeutic intervention are the cytochrome (cyt) bc1 complex, which is an essential component of the mitochondrial electron transport chain (...

    Heather J. Painter, Joanne M. Morrisey, Michael W. Mather, Lindsey M. Orchard, Cuyler Luck, Martin J. Smilkstein, Michael K. Riscoe, Akhil B. Vaidya, Manuel Llinás
  • Selection of Cytochrome <em>b</em> Mutants Is Rare among <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> Patients Failing Treatment with Atovaquone-Proguanil in Cambodia
    Mechanisms of Resistance
    Selection of Cytochrome b Mutants Is Rare among Plasmodium falciparum Patients Failing Treatment with Atovaquone-Proguanil in Cambodia

    Atovaquone-proguanil remains effective against multidrug-resistant Plasmodium falciparum in Southeast Asia, but resistance is mediated by a single point mutation in cytochrome b (cytb) that can arise during treatment. Among 14 atovaquone-proguanil treatment failures in a clinical trial in Cambodia, only one recrudescence harbored the cytb...

    Jessica T. Lin, Andreea Waltmann, Kara A. Moser, Zackary Park, Yu Bin Na, Ozkan Aydemir, Nicholas F. Brazeau, Panita Gosi, Patrick W. Marsh, Meredith S. Muller, Michele Spring, Somethy Sok, Jeffrey A. Bailey, David L. Saunders, Chanthap Lon, Mariusz Wojnarski
  • Open Access
    Defining the Antimalarial Activity of Cipargamin in Healthy Volunteers Experimentally Infected with Blood-Stage <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span>
    Clinical Therapeutics
    Defining the Antimalarial Activity of Cipargamin in Healthy Volunteers Experimentally Infected with Blood-Stage Plasmodium falciparum

    The spiroindolone cipargamin, a new antimalarial compound that inhibits Plasmodium ATP4, is currently in clinical development. This study aimed to characterize the antimalarial activity of cipargamin in healthy volunteers experimentally infected with blood-stage Plasmodium falciparum.

    James S. McCarthy, Azrin N. Abd-Rahman, Katharine A. Collins, Louise Marquart, Paul Griffin, Anne Kümmel, Aline Fuchs, Cornelis Winnips, Vishal Mishra, Katalin Csermak-Renner, J. Prakash Jain, Preetam Gandhi
  • Open Access
    <em>In Vivo</em> Efficacy and Metabolism of the Antimalarial Cycleanine and Improved <em>In Vitro</em> Antiplasmodial Activity of Semisynthetic Analogues
    Pharmacology
    In Vivo Efficacy and Metabolism of the Antimalarial Cycleanine and Improved In Vitro Antiplasmodial Activity of Semisynthetic Analogues

    Bisbenzylisoquinoline (BBIQ) alkaloids are a diverse group of natural products that demonstrate a range of biological activities. In this study, the in vitro antiplasmodial activity of three BBIQ alkaloids (cycleanine [compound 1], isochondodendrine [compound 2], and 2′-norcocsuline [compound 3]) isolated from the Triclisia subcordata Oliv. medicinal plant...

    Fidelia Ijeoma Uche, Xiaozhen Guo, Jude Okokon, Imran Ullah, Paul Horrocks, Joshua Boateng, Chenggang Huang, Wen-Wu Li
  • Open Access
    Transmission of Artemisinin-Resistant Malaria Parasites to Mosquitoes under Antimalarial Drug Pressure
    Mechanisms of Resistance
    Transmission of Artemisinin-Resistant Malaria Parasites to Mosquitoes under Antimalarial Drug Pressure

    Resistance to artemisinin-based combination therapy (ACT) in the Plasmodium falciparum parasite is threatening to reverse recent gains in reducing global deaths from malaria. While resistance manifests as delayed parasite clearance in patients, the phenotype can only spread geographically via the sexual stages and mosquito transmission. In addition to their asexual...

    Kathrin Witmer, Farah A. Dahalan, Michael J. Delves, Sabrina Yahiya, Oliver J. Watson, Ursula Straschil, Darunee Chiwcharoen, Boodtee Sornboon, Sasithon Pukrittayakamee, Richard D. Pearson, Virginia M. Howick, Mara K. N. Lawniczak, Nicholas J. White, Arjen M. Dondorp, Lucy C. Okell, Kesinee Chotivanich, Andrea Ruecker, Jake Baum
  • Regioisomerization of Antimalarial Drug WR99210 Explains the Inactivity of a Commercial Stock
    Chemistry; Biosynthesis
    Regioisomerization of Antimalarial Drug WR99210 Explains the Inactivity of a Commercial Stock

    WR99210, a former antimalarial drug candidate now widely used for the selection of Plasmodium transfectants, selectively targets the parasite’s dihydrofolate reductase thymidine synthase bifunctional enzyme (DHFR-TS) but not human DHFR, which is not fused with TS. Accordingly, WR99210 and plasmids expressing the human dhfr gene have become valued tools for the genetic modification of parasites in the laboratory....

    T. Parks Remcho, Sravanthi D. Guggilapu, Phillip Cruz, Glenn A. Nardone, Gavin Heffernan, Robert D. O’Connor, Carole A. Bewley, Thomas E. Wellems, Kristin D. Lane
  • Inhibition of PfMYST Histone Acetyltransferase Activity Blocks <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> Growth and Survival
    Mechanisms of Action: Physiological Effects
    Inhibition of PfMYST Histone Acetyltransferase Activity Blocks Plasmodium falciparum Growth and Survival

    One of the major barriers in the prevention and control of malaria programs worldwide is the growing emergence of multidrug resistance in Plasmodium parasites, and this necessitates continued efforts to discover and develop effective drug molecules targeting novel proteins essential for parasite survival. In recent years, epigenetic regulators have evolved as an attractive drug target option owing to their crucial role in...

    Utsav Sen, Akshaykumar Nayak, Juhi Khurana, Deepu Sharma, Ashish Gupta
  • Open Access
    Tolerance of Gambian <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> to Dihydroartemisinin and Lumefantrine Detected by <em>Ex Vivo</em> Parasite Survival Rate Assay
    Susceptibility
    Tolerance of Gambian Plasmodium falciparum to Dihydroartemisinin and Lumefantrine Detected by Ex Vivo Parasite Survival Rate Assay

    Monitoring of Plasmodium falciparum sensitivity to antimalarial drugs in Africa is vital for malaria elimination. However, the commonly used ex vivo/in vitro 50% inhibitory concentration (IC50) test gives inconsistent results for several antimalarials, while the alternative ring-stage survival assay (RSA) for artemisinin derivatives has...

    Haddijatou Mbye, Fatoumata Bojang, Aminata Seedy Jawara, Bekai Njie, Nuredin Ibrahim Mohammed, Joseph Okebe, Umberto D’Alessandro, Alfred Amambua-Ngwa
  • Associations between Malaria-Preventive Regimens and <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> Drug Resistance-Mediating Polymorphisms in Ugandan Pregnant Women
    Mechanisms of Resistance
    Associations between Malaria-Preventive Regimens and Plasmodium falciparum Drug Resistance-Mediating Polymorphisms in Ugandan Pregnant Women

    Intermittent preventive treatment in pregnancy (IPTp) with monthly sulfadoxine-pyrimethamine (SP) is recommended for malaria-endemic parts of Africa, but efficacy is compromised by resistance, and, in recent trials, dihydroartemisinin-piperaquine (DP) has shown better antimalarial protective efficacy. We utilized blood samples from a recent trial to evaluate selection by IPTp with DP or SP of...

    Patience Nayebare, Victor Asua, Melissa D. Conrad, Richard Kajubi, Abel Kakuru, Joaniter I. Nankabirwa, Dennis Muhanguzi, Grant Dorsey, Moses R. Kamya, Sam Nsobya, Philip J. Rosenthal
  • Prevalence of <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> Kelch 13 (<em>PfK13</em>) and Ubiquitin-Specific Protease 1 (<em>pfubp1</em>) Gene Polymorphisms in Returning Travelers from Africa Reported in Eastern China
    Epidemiology and Surveillance
    Prevalence of Plasmodium falciparum Kelch 13 (PfK13) and Ubiquitin-Specific Protease 1 (pfubp1) Gene Polymorphisms in Returning Travelers from Africa Reported in Eastern China

    Delayed clearance of Plasmodium falciparum by artemisinin-based combination therapies (ACTs) has already been observed for African isolates. Here, we aimed to investigate the prevalence, among travelers returning from African countries, of polymorphisms in two genes correlated with delayed parasite clearance (encoding...

    He Yan, Xiangli Kong, Tao Zhang, Huihui Xiao, Xinyu Feng, Hong Tu, Jun Feng

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