Judith Straimer
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View article: Cryo-EM structures of Nipah virus polymerases and high-throughput biochemical RdRp assay development enable anti-NiV drug discovery
Cryo-EM structures of Nipah virus polymerases and high-throughput biochemical RdRp assay development enable anti-NiV drug discovery Open
The transcription and replication of Nipah virus (NiV) is driven by the large protein (L) and its essential co-factor phosphoprotein (P). L encodes all the viral enzymatic functions including RNA-dependent RNA polymerase (RdRp) activity wh…
View article: Cryo-EM structures of Nipah virus polymerases and high-throughput RdRp assay development enable anti-NiV drug discovery
Cryo-EM structures of Nipah virus polymerases and high-throughput RdRp assay development enable anti-NiV drug discovery Open
Transcription and replication of the Nipah virus (NiV) are driven by the large protein (L) together with its essential co-factor phosphoprotein (P). L encodes all the viral enzymatic functions, including RNA-dependent RNA polymerase (RdRp)…
View article: Generation of a Transgenic Plasmodium cynomolgi Parasite Expressing Plasmodium vivax Circumsporozoite Protein for Testing P. vivax CSP-Based Malaria Vaccines in Non-Human Primates
Generation of a Transgenic Plasmodium cynomolgi Parasite Expressing Plasmodium vivax Circumsporozoite Protein for Testing P. vivax CSP-Based Malaria Vaccines in Non-Human Primates Open
Background/Objectives: Malaria, caused by infection with Plasmodium parasites, exacts a heavy toll worldwide. There are two licensed vaccines for malaria as well as two monoclonal antibodies that have shown promising efficacy in field tria…
View article: A conserved metabolic signature associated with response to fast-acting anti-malarial agents
A conserved metabolic signature associated with response to fast-acting anti-malarial agents Open
Characterizing the mode of action of anti-malarial compounds that emerge from high-throughput phenotypic screens is central to understanding how parasite resistance to these drugs can emerge. Here, we have employed untargeted metabolomics …
View article: A conserved metabolic signature associated with response to fast-acting antimalarial agents
A conserved metabolic signature associated with response to fast-acting antimalarial agents Open
Characterizing the mode of action of antimalarial compounds that emerge from high-throughput phenotypic screens is central to understanding how parasite resistance to these drugs can emerge. Here, we have employed untargeted metabolomics t…
View article: A G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin
A G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin Open
Diverse compounds target the Plasmodium falciparum Na + pump PfATP4, with cipargamin and (+)-SJ733 the most clinically-advanced. In a recent clinical trial for cipargamin, recrudescent parasites emerged, with most having a G358S mutation i…
View article: Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria
Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria Open
A series of 5-aryl-2-amino-imidazothiadiazole (ITD) derivatives were identified by a phenotype-based high-throughput screening using a blood stage Plasmodium falciparum (Pf) growth inhibition assay. A lead optimization program focused on i…
View article: Efficacy of Cipargamin (KAE609) in a Randomized, Phase II Dose-Escalation Study in Adults in Sub-Saharan Africa With Uncomplicated <i>Plasmodium falciparum</i> Malaria
Efficacy of Cipargamin (KAE609) in a Randomized, Phase II Dose-Escalation Study in Adults in Sub-Saharan Africa With Uncomplicated <i>Plasmodium falciparum</i> Malaria Open
Background Cipargamin (KAE609) is a potent antimalarial in a phase II trial. Here we report efficacy, pharmacokinetics, and resistance marker analysis across a range of cipargamin doses. These were secondary endpoints from a study primaril…
View article: Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness
Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness Open
The emergence of mutant K13-mediated artemisinin (ART) resistance in Plasmodium falciparum malaria parasites has led to widespread treatment failures across Southeast Asia. In Africa, K13- propeller genotyping confirms the emergence of the…
View article: High Prevalence of <i>Plasmodium falciparum</i> K13 Mutations in Rwanda Is Associated With Slow Parasite Clearance After Treatment With Artemether-Lumefantrine
High Prevalence of <i>Plasmodium falciparum</i> K13 Mutations in Rwanda Is Associated With Slow Parasite Clearance After Treatment With Artemether-Lumefantrine Open
In Southeast Asia, mutations in the Plasmodium falciparum K13 gene have led to delayed parasite clearance and treatment failures in patients with malaria receiving artemisinin combination therapies. Until recently, relevant K13 mutations h…
View article: Author response: Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness
Author response: Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness Open
Article Figures and data Abstract Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract The emergence of mutant K13-mediated artem…
View article: <i>P. falciparum</i>K13 mutations present varying degrees of artemisinin resistance and reduced fitness in African parasites
<i>P. falciparum</i>K13 mutations present varying degrees of artemisinin resistance and reduced fitness in African parasites Open
The emergence of artemisinin (ART) resistance in Plasmodium falciparum parasites, driven by K13 mutations, has led to widespread antimalarial treatment failure in Southeast Asia. In Africa, our genotyping of 3,299 isolates confirms the eme…
View article: <i>Plasmodium falciparum</i> K13 mutations in Africa and Asia present varying degrees of artemisinin resistance and an elevated fitness cost in African parasites
<i>Plasmodium falciparum</i> K13 mutations in Africa and Asia present varying degrees of artemisinin resistance and an elevated fitness cost in African parasites Open
The emergence of artemisinin (ART) resistance in Plasmodium falciparum parasites has led to increasing rates of treatment failure with first-line ART-based combination therapies (ACTs) in Southeast Asia. In this region, select mutations in…
Insights into the intracellular localization, protein associations and artemisinin resistance properties of Plasmodium falciparum K13 Open
The emergence of artemisinin (ART) resistance in Plasmodium falciparum intra-erythrocytic parasites has led to increasing treatment failure rates with first-line ART-based combination therapies in Southeast Asia. Decreased parasite suscept…
View article: Generation of Transgenic Human Malaria Parasites With Strong Fluorescence in the Transmission Stages
Generation of Transgenic Human Malaria Parasites With Strong Fluorescence in the Transmission Stages Open
Malaria parasites have a complex life cycle that includes specialized stages for transmission between their mosquito and human hosts. These stages are an understudied part of the lifecycle yet targeting them is an essential component of th…
View article: Artemisinin resistance phenotypes and K13 inheritance in a <i>Plasmodium falciparum</i> cross and <i>Aotus</i> model
Artemisinin resistance phenotypes and K13 inheritance in a <i>Plasmodium falciparum</i> cross and <i>Aotus</i> model Open
Significance Artemisinin-based combination therapies (ACTs) are first-line antimalarial therapies used worldwide. The artemisinin drug (ART) component clears the bulk of infection rapidly, but small numbers of persistent parasites must be …
View article: <i>Plasmodium falciparum</i> K13 Mutations Differentially Impact Ozonide Susceptibility and Parasite Fitness <i>In Vitro</i>
<i>Plasmodium falciparum</i> K13 Mutations Differentially Impact Ozonide Susceptibility and Parasite Fitness <i>In Vitro</i> Open
The emergence and spread in Southeast Asia of Plasmodium falciparum resistance to artemisinin (ART) derivatives, the cornerstone of first-line artemisinin-based combination therapies (ACTs), underscore the urgent need to identify suitable …
View article: Correlation of the observed survival or antimalarial activity versus modeled maximal effect relationship.
Correlation of the observed survival or antimalarial activity versus modeled maximal effect relationship. Open
Correlation of the observed survival or antimalarial activity versus modeled maximal effect relationship.
View article: In vitro activity against a panel of resistant and sensitive strains of <i>P</i>. <i>falciparum</i>.
In vitro activity against a panel of resistant and sensitive strains of <i>P</i>. <i>falciparum</i>. Open
In vitro activity against a panel of resistant and sensitive strains of P. falciparum.
View article: Parasite Reduction Ratio.
Parasite Reduction Ratio. Open
The number of viable P. falciparum strain 3D7 (MR4) versus treatment time is compared between ACT-451840 and a selection of standard antimalarials (data for the latter was previously reported in reference [24]). Data are the mean ± SD of f…
View article: Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose–Efficacy Modeling
Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose–Efficacy Modeling Open
Background Artemisinin resistance observed in Southeast Asia threatens the continued use of artemisinin-based combination therapy in endemic countries. Additionally, the diversity of chemical mode of action in the global portfolio of marke…
View article: A Worldwide Map of<i>Plasmodium falciparum</i>K13-Propeller Polymorphisms
A Worldwide Map of<i>Plasmodium falciparum</i>K13-Propeller Polymorphisms Open
No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisin…
View article: Targeting the Cell Stress Response of Plasmodium falciparum to Overcome Artemisinin Resistance
Targeting the Cell Stress Response of Plasmodium falciparum to Overcome Artemisinin Resistance Open
Successful control of falciparum malaria depends greatly on treatment with artemisinin combination therapies. Thus, reports that resistance to artemisinins (ARTs) has emerged, and that the prevalence of this resistance is increasing, are a…