Dataset Information

A Novel Antiparasitic Compound Kills Ring-Stage Plasmodium falciparum and Retains Activity Against Artemisinin-Resistant Parasites.

ABSTRACT: Spreading antimalarial resistance threatens effective treatment of malaria, an infectious disease caused by Plasmodium parasites. We identified a compound, BCH070, that inhibits asexual growth of multiple antimalarial-resistant strains of Plasmodium falciparum (half maximal inhibitory concentration [IC50] = 1-2 µM), suggesting that BCH070 acts via a novel mechanism of action. BCH070 preferentially kills early ring-form trophozoites, and, importantly, equally inhibits ring-stage survival of wild-type and artemisinin-resistant parasites harboring the PfKelch13:C580Y mutation. Metabolomic analysis demonstrates that BCH070 likely targets multiple pathways in the parasite. BCH070 is a promising lead compound for development of new antimalarial combination therapy that retains activity against artemisinin-resistant parasites.

SUBMITTER: Clements RL

PROVIDER: S-EPMC7050989 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Novel Antiparasitic Compound Kills Ring-Stage Plasmodium falciparum and Retains Activity Against Artemisinin-Resistant Parasites.

Clements Rebecca L RL Streva Vincent V Dumoulin Peter P Huang Weigang W Owens Edward E Raj Dipak K DK Burleigh Barbara B Llinás Manuel M Winzeler Elizabeth A EA Zhang Qisheng Q Dvorin Jeffrey D JD

The Journal of infectious diseases 20200301 6

Spreading antimalarial resistance threatens effective treatment of malaria, an infectious disease caused by Plasmodium parasites. We identified a compound, BCH070, that inhibits asexual growth of multiple antimalarial-resistant strains of Plasmodium falciparum (half maximal inhibitory concentration [IC50] = 1-2 µM), suggesting that BCH070 acts via a novel mechanism of action. BCH070 preferentially kills early ring-form trophozoites, and, importantly, equally inhibits ring-stage survival of wild- ...[more]

PMID: 31616928

Similar Datasets

Project description:BackgroundMalaria control in sub-Saharan Africa relies upon prompt case management with artemisinin-based combination therapy (ACT). Ring-stage parasite mRNA, measured by sbp1 quantitative reverse-transcriptase PCR (qRT-PCR), was previously reported to persist after ACT treatment and hypothesized to reflect temporary arrest of the growth of ring-stage parasites (dormancy) following exposure to artemisinins. Here, the persistence of ring-stage parasitaemia following ACT and non-ACT treatment was examined.MethodsSamples were used from naturally infected Malian gametocyte carriers who received dihydroartemisinin-piperaquine (DP) or sulfadoxine-pyrimethamine (SP-AQ) with or without gametocytocidal drugs. Gametocytes and ring-stage parasites were quantified by qRT-PCR during 42 days of follow-up.ResultsAt baseline, 89% (64/73) of participants had measurable ring-stage parasite mRNA. Following treatment, the proportion of ring-stage parasite-positive individuals and estimated densities declined for all four treatment groups. Ring-stage parasite prevalence and density was generally lower in arms that received DP compared to SP-AQ. This finding was most apparent days 1, 2, and 42 of follow-up (p?<?0.01). Gametocytocidal drugs did not influence ring-stage parasite persistence. Ring-stage parasite density estimates on days 14 and 28 after initiation of treatment were higher among individuals who subsequently experienced recurrent parasitaemia compared to those who remained free of parasites until day 42 after initiation of treatment (pday 14?=?0.011 and pday 28?=?0.068). No association of ring-stage persistence with gametocyte carriage was observed.ConclusionsThe current findings of lower ring-stage persistence after ACT without an effect of gametocytocidal partner drugs affirms the use of sbp1 as ring-stage marker. Lower persistence of ring-stage mRNA after ACT treatment suggests the marker may not reflect dormant parasites whilst it was predictive of re-appearance of parasitaemia.

Dataset Information

A Novel Antiparasitic Compound Kills Ring-Stage Plasmodium falciparum and Retains Activity Against Artemisinin-Resistant Parasites.

Publications

A Novel Antiparasitic Compound Kills Ring-Stage Plasmodium falciparum and Retains Activity Against Artemisinin-Resistant Parasites.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets