Open Access. Powered by Scholars. Published by Universities.®
Immunology and Infectious Disease Commons™
Open Access. Powered by Scholars. Published by Universities.®
- Keyword
-
- Amino Acid (1)
- Amino Acid Sequence (1)
- Animals (1)
- Antimalarials (1)
- Artemether-lumefantrine (1)
-
- Boron Compounds (1)
- CRISPR-Cas Systems (1)
- Catalytic Domain (1)
- Cleavage And Polyadenylation Specificity Factor (1)
- Dihydroartemisinin-piperaquine (1)
- Drug Resistance (1)
- Drug resistance (1)
- Erythrocytes (1)
- Falciparum (1)
- Gene Editing (1)
- Humans (1)
- Malaria (1)
- Malaria, Falciparum (1)
- Messenger (1)
- Mice (1)
- Molecular Docking Simulation (1)
- Mutation (1)
- Plasmodium berghei (1)
- Protein Binding (1)
- Protein Interaction Domains and Motifs (1)
- Protein Structure (1)
- Protein Structure, Secondary (1)
- Protozoan Proteins (1)
- RNA (1)
- Publication
- Publication Type
Articles 1 - 2 of 2
Full-Text Articles in Immunology and Infectious Disease
Changing Antimalarial Drug Sensitivities In Uganda, Stephanie Alexis Rasmussen
Changing Antimalarial Drug Sensitivities In Uganda, Stephanie Alexis Rasmussen
Dissertations, Masters Theses, Capstones, and Culminating Projects
Dihydroartemisinin-piperaquine (DP) has demonstrated excellent efficacy for the treatment and prevention of malaria in Uganda. However, resistance to both components of this regimen has emerged in Southeast Asia. The efficacy of artemether-lumefantrine, the first-line regimen to treat malaria in Uganda, has also been excellent, but continued pressure may select for parasites with decreased sensitivity to lumefantrine. To gain insight into current drug sensitivity patterns, ex vivo sensitivities were assessed and genotypes previously associated with altered drug sensitivity were characterized for 58 isolates collected in Tororo, Uganda from subjects presenting in 2016 with malaria from the community or as part of …
A Potent Antimalarial Benzoxaborole Targets A Plasmodium Falciparum Cleavage And Polyadenylation Specificity Factor Homologue., Ebere Sonoiki, Caroline L. Ng, Marcus C. S. Lee, Denghui Guo, Yong-Kang Zhang, Yasheen Zhou, M. R. K. Alley, Vida Ahyong, Laura M. Sanz, Maria Jose Lafuente-Monasterio, Chen Dong, Patrick G. Schupp, Jiri Gut, Jenny Legac, Roland A. Cooper, Francisco-Javier Gamo, Joseph Derisi, Yvonne R. Freund, David A. Fidock, Philip J. Rosenthal
A Potent Antimalarial Benzoxaborole Targets A Plasmodium Falciparum Cleavage And Polyadenylation Specificity Factor Homologue., Ebere Sonoiki, Caroline L. Ng, Marcus C. S. Lee, Denghui Guo, Yong-Kang Zhang, Yasheen Zhou, M. R. K. Alley, Vida Ahyong, Laura M. Sanz, Maria Jose Lafuente-Monasterio, Chen Dong, Patrick G. Schupp, Jiri Gut, Jenny Legac, Roland A. Cooper, Francisco-Javier Gamo, Joseph Derisi, Yvonne R. Freund, David A. Fidock, Philip J. Rosenthal
Natural Sciences and Mathematics | Faculty Scholarship
Benzoxaboroles are effective against bacterial, fungal and protozoan pathogens. We report potent activity of the benzoxaborole AN3661 against Plasmodium falciparum laboratory-adapted strains (mean IC50 32 nM), Ugandan field isolates (mean ex vivo IC50 64 nM), and murine P. berghei and P. falciparum infections (day 4 ED90 0.34 and 0.57 mg kg-1, respectively). Multiple P. falciparum lines selected in vitro for resistance to AN3661 harboured point mutations in pfcpsf3, which encodes a homologue of mammalian cleavage and polyadenylation specificity factor subunit 3 (CPSF-73 or CPSF3). CRISPR-Cas9-mediated introduction of pfcpsf3 mutations into parental lines recapitulated AN3661 resistance. PfCPSF3 homology models placed these …