Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics

…, S Bopp, VC Corey, NF Gnädig, O Coburn-Flynn… - Science, 2018 - science.org
Chemogenetic characterization through in vitro evolution combined with whole-genome
analysis can identify antimalarial drug targets and drug-resistance genes. We performed a …

[PDF][PDF] Profiling the essential nature of lipid metabolism in asexual blood and gametocyte stages of Plasmodium falciparum

…, MCS Lee, N Spottiswoode, O Coburn-Flynn… - Cell host & …, 2015 - cell.com
During its life cycle, Plasmodium falciparum undergoes rapid proliferation fueled by de novo
synthesis and acquisition of host cell lipids. Consistent with this essential role, Plasmodium …

[HTML][HTML] A broad analysis of resistance development in the malaria parasite

…, O Coburn-Flynn, T Sakata-Kato, O Fuchs… - Nature …, 2016 - nature.com
… Two of the mutations, G131S and Y126C, were contained in the Q o site, while the third
mutation (V284L) was not in either the Q o or Q i binding region 29 . G131S was also the major …

[HTML][HTML] Triaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate

…, MS Martínez, LM Sanz, O Coburn-Flynn… - Nature …, 2015 - nature.com
The widespread emergence of Plasmodium falciparum (Pf) strains resistant to frontline
agents has fuelled the search for fast-acting agents with novel mechanism of action. Here, we …

Balancing drug resistance and growth rates via compensatory mutations in the Plasmodium falciparum chloroquine resistance transporter

…, DJ Johnson, O CoburnFlynn… - Molecular …, 2015 - Wiley Online Library
The widespread use of chloroquine to treat P lasmodium falciparum infections has resulted
in the selection and dissemination of variant haplotypes of the primary resistance …

[PDF][PDF] The Plasmodium falciparum ABC transporter ABCI3 confers parasite strain-dependent pleiotropic antimalarial drug resistance

…, T Yeo, S Mok, AY Burkhard, O Coburn-Flynn… - Cell chemical …, 2022 - cell.com
Widespread Plasmodium falciparum resistance to first-line antimalarials underscores the vital
need to develop compounds with novel modes of action and identify new druggable targets…

N-Aryl-2-aminobenzimidazoles: Novel, Efficacious, Antimalarial Lead Compounds

…, D Waterson, MCS Lee, O Coburn-Flynn… - Journal of Medicinal …, 2014 - ACS Publications
From the phenotypic screening of the AstraZeneca corporate compound collection, N-aryl-2-aminobenzimidazoles
have emerged as novel hits against the asexual blood stage of …

[PDF][PDF] Structure-Guided identification of resistance breaking antimalarial n‑myristoyltransferase inhibitors

AC Schlott, S Mayclin, AR Reers, O Coburn-Flynn… - Cell Chemical …, 2019 - cell.com
The attachment of myristate to the N-terminal glycine of certain proteins is largely a co-translational
modification catalyzed by N-myristoyltransferase (NMT), and involved in protein …

Yeast-Based High-Throughput Screen Identifies Plasmodium falciparum Equilibrative Nucleoside Transporter 1 Inhibitors That Kill Malaria Parasites

…, RD Moir, SH Adjalley, O Coburn-Flynn… - ACS chemical …, 2015 - ACS Publications
Equilibrative transporters are potential drug targets; however, most functional assays involve
radioactive substrate uptake that is unsuitable for high-throughput screens (HTS). We …

[HTML][HTML] A large self-transmissible resistance plasmid from Nigeria contains genes that ameliorate a carrying cost

R Monárrez, M Braun, O Coburn-Flynn, J Botelho… - Scientific Reports, 2019 - nature.com
Antimicrobial resistance is rapidly expanding, in a large part due to mobile genetic elements.
We screened 94 fecal fluoroquinolone-resistant Escherichia coli isolates from Nigeria for …