Antiparasitic agents articles within Nature Communications

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  • Article
    | Open Access

    Malaria parasites from patients who fail atovaquone therapies are highly drug-resistant, with mutations at Y268 in cytochrome b. Here the authors show that this mutation results in multiple defects in the parasite’s development and prevents transmission from mosquitoes to mice.

    • Victoria A. Balta
    • , Deborah Stiffler
    •  & Theresa A. Shapiro

  • Article
    | Open Access

    Microsporidia are fungal-related intracellular parasites that infect animals and humans. Here, Murareanu et al. develop a high-throughput screening method using the nematode C. elegans as a host, and identify several compounds that inhibit microsporidia infection through different mechanisms.

    • Brandon M. Murareanu
    • , Noelle V. Antao
    •  & Aaron W. Reinke

  • Comment
    | Open Access

    Malaria cases and deaths remain unacceptably high and are resurgent in several settings, though recent developments inspire optimism. This includes the approval of the world’s first malaria vaccine and results from novel vaccine candidates and trials testing innovative combinatorial interventions.

    • Prasanna Jagannathan
    •  & Abel Kakuru

  • Article
    | Open Access

    Here, de Vries et al. perform a pre-clinical characterization of the antimalarial compound MMV693183: the compound targets acetyl-CoA synthetase, has efficacy in humanized mice against Plasmodium falciparum infection, blocks transmission to mosquito vectors, is safe in rats, and pharmacokinetic-pharmacodynamic modeling informs about a potential oral human dosing regimen.

    • Laura E. de Vries
    • , Patrick A. M. Jansen
    •  & Koen J. Dechering

  • Article
    | Open Access

    Here, Reader et al. screen the Medicines for Malaria Venture Pandemic Response Box in parallel against Plasmodiumasexual and liver stage parasites, stage IV/V gametocytes, gametes, oocysts and as endectocides. They identify two potent transmission-blocking drugs: a histone demethylase inhibitor ML324 and the antitubercular SQ109.

    • Janette Reader
    • , Mariëtte E. van der Watt
    •  & Lyn-Marié Birkholtz

  • Article
    | Open Access

    Primaquine (PQ) is a widely used anti-malaria drug, but its mechanism of action is unclear. Here, Camarda et al. show that PQ’s activity against liver and sexual Plasmodium stages depends on generation of hydroxylated-PQ metabolites (OH-PQm), which, undergoing further reactions, results in production of H2O2.

    • Grazia Camarda
    • , Piyaporn Jirawatcharadech
    •  & Giancarlo A. Biagini

  • Article
    | Open Access

    Sexual forms of malaria parasites are responsible for transmission to the mosquito. Anti-malarial drug resistance remains a serious problem and requires advent of new drug therapies. Here, the authors present a high-throughput screen of potential antimalarial compounds, identifying seventeen drug-like molecules specifically targeting transmission.

    • Michael J. Delves
    • , Celia Miguel-Blanco
    •  & Jake Baum

  • Article
    | Open Access

    Artemisinin (ART) is a widely used antimalarial drug, but its mechanism of action is poorly understood. Here, Bridgford et al. show that ART kills parasites by a two-pronged mechanism, causing protein damage and compromising proteasome function, and that accumulation of proteasome substrates activates the ER stress response.

    • Jessica L. Bridgford
    • , Stanley C. Xie
    •  & Leann Tilley

  • Article
    | Open Access

    Increasing resistance of Plasmodium falciparum strains to piperaquine (PPQ) in Southeast Asia is of concern and resistance mechanisms are incompletely understood. Here, Ross et al. show that mutations in the P. falciparum chloroquine resistance transporter are rapidly increasing in prevalence in Cambodia and confer resistance to PPQ.

    • Leila S. Ross
    • , Satish K. Dhingra
    •  & David A. Fidock

  • Article
    | Open Access

    Piperaquine (PPQ) resistance of Plasmodium is an increasing problem. Here, Bopp et al. find a bimodal dose−response curve of Cambodian isolates exposed to PPQ, with the area under the curve correlating with in vitro PPQ resistance, and show the importance of Plasmepsin II–III copy number to PPQ resistance.

    • Selina Bopp
    • , Pamela Magistrado
    •  & Sarah K. Volkman

  • Article
    | Open Access

    Malaria transmission is effected by intra-erythrocytic parasites that commit to sexual development and form gametocytes. Here, the authors show that early reticulocytes in the major sites of haematopoiesis establish a cryptic asexual cycle; this cycle is characterised by early preferential commitment to gametocytogenesis, which initiates malaria transmission and drug resistance.

    • Rebecca S. Lee
    • , Andrew P. Waters
    •  & James M. Brewer

  • Article
    | Open Access

    Pepstatin is a known inhibitor of malarial proteases, but its activity varies between sources. Here, Istvanet al. identify a pepstatin ester as the active component of pepstatin preparations and show that this prodrug is activated by a Plasmodiumesterase, mutation of which can confer resistance to pepstatin and other compounds.

    • Eva S. Istvan
    • , Jeremy P. Mallari
    •  & Daniel E. Goldberg

  • Article
    | Open Access

    The emergence of resistant Plasmodiumstrains fuels the search for new antimalarials. Here, the authors present a new class of potent antimalarial compounds, the triaminopyrimidines, that display low toxicity and long half-life in animal models.

    • Shahul Hameed P.
    • , Suresh Solapure
    •  & Vasan K. Sambandamurthy

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