Malaria Drug Accelerator (MalDA)

The Malaria Drug Accelerator (MalDA) is a collaboration of 15 scientific laboratories funded by the Bill and Melinda Gates foundation to advance the development of new antimalarial drugs.

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Who are we?

The MALDA Consortium is an innovative target-guided discovery platform linking phenotypic hits to function for malaria. MALDA offers a new research paradigm that compliments the existing ways malaria drugs are discovered: A virtual pharmaceutical company.

How do we work together?

The MALDA Consortium is a collaboration between fifteen international groups, funded by BMGF.

MalDA Members

State-of-the-art
Plasmodium-adapted
technology platforms






In vitro selections
    State-of-Art Bioinformatics
    chemoinformatics / SAR / cryoEM
Conditional knockdown studies
     Essentiality assays
CRISPR-Cas9 reverse engineering
     Bar coded cell lines
     Overexpression lines
Metabolomics/Lipidomics/RNA-seq
     Macromolecule biosynthesis inhibitor assays
In vivo resistance evaluation

In vitro selections

  1. Clone by limiting dilution
  2. Select in triplicate
  3. Clone again
  4. Whole Genome Sequencing
  5. Compare genomes

External data
ChEMBL deposition data
Sequencing deposition data
Protocols

MalDA Publications

  1. Vanaerschot, M, Murithi, JM, Pasaje, CFA, Ghidelli-Disse, S, Dwomoh, L, Bird, M et al.. Inhibition of Resistance-Refractory P. falciparum Kinase PKG Delivers Prophylactic, Blood Stage, and Transmission-Blocking Antiplasmodial Activity. Cell Chem Biol. 2020;27 (7):806-816.e8. doi: 10.1016/j.chembiol.2020.04.001. PubMed PMID:32359426 PubMed Central PMC7369637.
  2. LaMonte, GM, Rocamora, F, Marapana, DS, Gnädig, NF, Ottilie, S, Luth, MR et al.. Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway. Nat Commun. 2020;11 (1):1780. doi: 10.1038/s41467-020-15440-4. PubMed PMID:32286267 PubMed Central PMC7156427.
  3. Abraham, M, Gagaring, K, Martino, ML, Vanaerschot, M, Plouffe, DM, Calla, J et al.. Probing the Open Global Health Chemical Diversity Library for Multistage-Active Starting Points for Next-Generation Antimalarials. ACS Infect Dis. 2020;6 (4):613-628. doi: 10.1021/acsinfecdis.9b00482. PubMed PMID:32078764 PubMed Central PMC7155171.
  4. Murithi, JM, Owen, ES, Istvan, ES, Lee, MCS, Ottilie, S, Chibale, K et al.. Combining Stage Specificity and Metabolomic Profiling to Advance Antimalarial Drug Discovery. Cell Chem Biol. 2020;27 (2):158-171.e3. doi: 10.1016/j.chembiol.2019.11.009. PubMed PMID:31813848 PubMed Central PMC7031696.
  5. Mandt, REK, Lafuente-Monasterio, MJ, Sakata-Kato, T, Luth, MR, Segura, D, Pablos-Tanarro, A et al.. In vitro selection predicts malaria parasite resistance to dihydroorotate dehydrogenase inhibitors in a mouse infection model. Sci Transl Med. 2019;11 (521):. doi: 10.1126/scitranslmed.aav1636. PubMed PMID:31801884 PubMed Central PMC7444640.
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MalDA selections

  • 200+ compounds under investigation
  • 400+ resistant clones generated for 58 compounds, and whole genome sequenced
  • 1300+ single nucleotide variants, 700+ indels, and 160+ copy number variants observed
  • At least 23 potential drug targets and 14 potential resistance genes identified or re-discovered using this method

Targets

  • PFK9
  • RFC4
  • ARK1
  • ATP4
  • KRS
  • cyto-IRS
  • FTB
  • PIP5K
  • ACS11
  • APP
  • DHFR-TS
  • PI4K
  • ATPase2
  • FP2A
  • NCR1
  • cPheRS
  • DHODH
  • RRB1
  • DPAP1
  • PRS

Resistance Genes

  • MFR3
  • ABCI3
  • CARL
  • MDR1
  • AAT1
  • CRT
  • PARE
  • YHM2
  • NEK1
  • MRP2
  • TKL3
  • CAF16
  • SulP
  • PF3D7_0909700

Compounds under consideration

  • 2,7-dibromo
    Cryptolepine hydrochloride (analog)
  • ACT-451840
  • Altiratinib
  • Anacetrapib
  • artemether
  • Atovaquone
  • AZ412
  • BI-1230
  • BI-1388
  • BI-2536
  • BRD1095
  • BRD3444
  • Brefeldin A
  • CEP-37440
  • cladosporin
  • Clofazimine
  • Cryptolepine hydrochloride
  • DDD01025389
  • DDD01057375
  • DDD01061024
  • DDD01250400
  • DDD01254473
  • DDD01298810
  • Decoquinate
  • Desoxyepothilone B
  • DSM265
  • ELQ300
  • GNF-Pf-1618
  • GNF-Pf-2740
  • GNF-Pf-2775
  • GNF-Pf-3582
  • GNF-Pf-3600
  • GNF-Pf-3703
  • GNF-Pf-4216
  • GNF-Pf-4283
  • GNF-Pf-445
  • GNF-Pf-4492
  • GNF-Pf-4577
  • GNF-Pf-5129
  • GNF-pf-5310
  • GNF-Pf-5349
  • GNF-Pf-5458
  • GNF-Pf-5611
  • GNF-Pf-5648
  • GNF-pf-5660
  • GNF-Pf-5666
  • GNF-pf-5668
  • GNF-Pf-5675
  • GNF179
  • GNF452
  • GNF707
  • indolmycin
  • Ivermectin
  • KAE609
  • KAF156
  • KAI407
  • KDU691
  • Lomitapide
  • lopinavir
  • Mefloquine
  • milciclib maleate
  • MMV000248
  • MMV000442
  • MMV000478
  • MMV000570
  • MMV000787
  • MMV006169
  • MMV006172
  • MMV006357
  • MMV006455
  • MMV006767
  • MMV006833
  • MMV006901
  • MMV006962
  • MMV007181
  • MMV007224
  • MMV007564
  • MMV008149
  • MMV009063
  • MMV009108
  • MMV010545
  • MMV011438
  • MMV011772
  • MMV011895
  • MMV011903
  • MMV019017
  • MMV019066
  • MMV019189
  • MMV019313
  • MMV019555
  • MMV019662
  • MMV019719
  • MMV019721
  • MMV019881
  • MMV019993
  • MMV020623
  • MMV020746
  • MMV020750
  • MMV021735
  • MMV022224
  • MMV022478
  • MMV023367
  • MMV023388
  • MMV023949
  • MMV023985
  • MMV024038
  • MMV024114
  • MMV024406
  • MMV026596
  • MMV027496
  • MMV027634
  • MMV028038
  • MMV028895
  • MMV029272
  • MMV030084
  • MMV030666
  • MMV032967
  • MMV064286
  • MMV084864
  • MMV084978
  • MMV085071
  • MMV085203
  • MMV1007245
  • MMV1010248
  • MMV1029508
  • MMV1030932
  • MMV1042937
  • MMV1044457
  • MMV1068987
  • MMV1079594
  • MMV1088520
  • MMV1091186
  • MMV1094822
  • MMV1147256
  • MMV1214532
  • MMV1223789
  • MMV1271410
  • MMV1291222
  • MMV1312865
  • MMV1317269
  • MMV1319550
  • MMV1371622
  • MMV1385304
  • MMV1394623
  • MMV1421890
  • MMV1425891
  • MMV1427995
  • MMV1430193
  • MMV1431916
  • MMV1432165
  • MMV1432711
  • MMV1449124
  • MMV1451822
  • MMV1454442
  • MMV1458543
  • MMV1468363
  • MMV1490397
  • MMV1490405
  • MMV1490583
  • MMV1501496
  • MMV1528403
  • MMV1531441
  • MMV396736
  • MMV396797
  • MMV407834
  • MMV665785
  • MMV665789
  • MMV665794
  • MMV665824
  • MMV665852
  • MMV665882
  • MMV665888
  • MMV665924
  • MMV665928
  • MMV665939
  • MMV665941
  • MMV665943
  • MMV665971
  • MMV666080
  • MMV666687
  • MMV667491
  • MMV668311
  • MMV668399
  • MMV673482
  • MMV673964
  • MMV675939
  • MMV676380
  • MMV676881
  • Naphthoquine
  • Neu-1029
  • NEU-1931
  • NEU-4995
  • NITD678
  • OSM-S-106
  • Pentamidine isothionate
  • pepstatin butyl ester
  • Piperaquine
  • primaquine
  • Puromycin
  • Sapanisertib
  • SQ109
  • Suloctidil
  • TCMDC-124553
  • TCMDC-135051
  • TCMDC-135395
  • Tryptanthrin
  • Velpatasvir
  • Verapamil
  • ZSTK-474
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