Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics
Chemogenetic characterization through in vitro evolution combined with whole-genome
analysis can identify antimalarial drug targets and drug-resistance genes. We performed a …
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 …
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 …
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 …
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 Coburn‐Flynn… - 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 …
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
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…
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 …
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 …
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 …
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 …
We screened 94 fecal fluoroquinolone-resistant Escherichia coli isolates from Nigeria for …