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. Mandt, REK, Luth, MR, Tye, MA, Mazitschek, R, Ottilie, S, Winzeler, EA et al.. Diverse evolutionary pathways challenge the use of collateral sensitivity as a strategy to suppress resistance. Elife. 2023;12 :. doi: 10.7554/eLife.85023. PubMed PMID:37737220 .
  2. Siqueira-Neto, JL, Wicht, KJ, Chibale, K, Burrows, JN, Fidock, DA, Winzeler, EA et al.. Antimalarial drug discovery: progress and approaches. Nat Rev Drug Discov. 2023; :. doi: 10.1038/s41573-023-00772-9. PubMed PMID:37652975 .
  3. Tilley, L, Xie, S, Wang, Y, Morton, C, Metcalfe, R, Dogovski, C et al.. Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase. Res Sq. 2023; :. doi: 10.21203/rs.3.rs-3198291/v1. PubMed PMID:37546892 PubMed Central PMC10402266.
  4. Kümpornsin, K, Kochakarn, T, Yeo, T, Okombo, J, Luth, MR, Hoshizaki, J et al.. Generation of a mutator parasite to drive resistome discovery in Plasmodium falciparum. Nat Commun. 2023;14 (1):3059. doi: 10.1038/s41467-023-38774-1. PubMed PMID:37244916 PubMed Central PMC10224993.
  5. Bopp, S, Pasaje, CFA, Summers, RL, Magistrado-Coxen, P, Schindler, KA, Corpas-Lopez, V et al.. Potent acyl-CoA synthetase 10 inhibitors kill Plasmodium falciparum by disrupting triglyceride formation. Nat Commun. 2023;14 (1):1455. doi: 10.1038/s41467-023-36921-2. PubMed PMID:36927839 PubMed Central PMC10020447.
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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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    Message us for inquiries regarding the MalDA project: ewinzeler@health.ucsd.edu

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