Supplementary Materials

Open-source discovery of chemical leads for next-generation chemoprotective antimalarials

Yevgeniya Antonova-Koch, Stephan Meister, Matthew Abraham, Madeline R. Luth, Sabine Ottilie, Amanda K. Lukens, Tomoyo Sakata-Kato, Manu Vanaerschot, Edward Owen, Juan Carlos Jado Rodriguez, Steven P. Maher, Jaeson Calla, David Plouffe Yang Zhong, Kaisheng Chen, Victor Chaumeau, Amy J. Conway, Case W. McNamara, Maureen Ibanez, Kerstin Gagaring, Fernando Neria Serrano, Korina Eribez, Cullin McLean Taggard, Andrea L. Cheung, Christie Lincoln, Biniam Ambachew, Melanie Rouillier, Dionicio Siegel, François Nosten, Dennis E. Kyle, Francisco-Javier Gamo, Yingyao Zhou, Manuel Llinás, David A. Fidock, Dyann F. Wirth, Jeremy Burrows, Brice Campo, Elizabeth A. Winzeler

Materials/Methods, Supplementary Text, Tables, Figures, and/or References

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  • Materials and Methods
  • Figs. S1 to S4
  • Tables S1 to S8
  • References
Data File S1
Compounds previously identified in high content imaging assays (9). The 197 compounds shared with this study were initially identified in an P. falciparum ABS assay (ABS-Sybr) and then retested against Plasmodium. yoelii hepatic stages (9). The file shows data from the previous publication, including whether the compound was a "hit" in the P. yoelii high content liver stage assay, whether it was selected for powder-resupply dose response testing in the high content P. yoelii assay (based on percent inhibition and compound availability), as well as the primary Pbluc and HepG2tox percent inhibition data from this study.
Data File S2
Clustering results. The file contains names, structures and cluster number for all compounds that are structurally similar to compounds with >83% inhibition in Pbluc. Also included are structure displays for 405 compounds from 68 clusters that show a p-value <= 0.05, cluster size >= 4 and hit fraction >= 0.75 are which are presented in Fig. 2.
Data File S3
Reconfirmation Set. File contains names, structures, and % inhibition in primary screen as well as dose response in secondary tests
Data File S4
Repurchased Validation Set (631 Compounds). Compounds selected for third round characterization
Data File S5
Metabolomic data. The file contains raw metabolomic data used to create metaprints.
Data File S6
Sequencing Data. The file contains whole genome sequencing variant detection files
Data File S7
Mitochondrial inhibition data. Dose response curves for compounds active in the D10-ScDHODH high-throughput (1536-well) assay. The attached Excel spreadsheet shows values for the 631 compounds (Repurchased Validation Set) plus two controls (atovaquone and artemisinin)