Nature Communications (Apr 2022)
Preclinical characterization and target validation of the antimalarial pantothenamide MMV693183
- Laura E. de Vries,
- Patrick A. M. Jansen,
- Catalina Barcelo,
- Justin Munro,
- Julie M. J. Verhoef,
- Charisse Flerida A. Pasaje,
- Kelly Rubiano,
- Josefine Striepen,
- Nada Abla,
- Luuk Berning,
- Judith M. Bolscher,
- Claudia Demarta-Gatsi,
- Rob W. M. Henderson,
- Tonnie Huijs,
- Karin M. J. Koolen,
- Patrick K. Tumwebaze,
- Tomas Yeo,
- Anna C. C. Aguiar,
- Iñigo Angulo-Barturen,
- Alisje Churchyard,
- Jake Baum,
- Benigno Crespo Fernández,
- Aline Fuchs,
- Francisco-Javier Gamo,
- Rafael V. C. Guido,
- María Belén Jiménez-Diaz,
- Dhelio B. Pereira,
- Rosemary Rochford,
- Camille Roesch,
- Laura M. Sanz,
- Graham Trevitt,
- Benoit Witkowski,
- Sergio Wittlin,
- Roland A. Cooper,
- Philip J. Rosenthal,
- Robert W. Sauerwein,
- Joost Schalkwijk,
- Pedro H. H. Hermkens,
- Roger V. Bonnert,
- Brice Campo,
- David A. Fidock,
- Manuel Llinás,
- Jacquin C. Niles,
- Taco W. A. Kooij,
- Koen J. Dechering
Affiliations
- Laura E. de Vries
- Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center
- Patrick A. M. Jansen
- Department of Dermatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center
- Catalina Barcelo
- Medicines for Malaria Venture
- Justin Munro
- Department of Chemistry and Huck Center for Malaria Research, The Pennsylvania State University
- Julie M. J. Verhoef
- Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center
- Charisse Flerida A. Pasaje
- Department of Biological Engineering, Massachusetts Institute of Technology
- Kelly Rubiano
- Department of Microbiology & Immunology, Columbia University Irving Medical Center
- Josefine Striepen
- Department of Microbiology & Immunology, Columbia University Irving Medical Center
- Nada Abla
- Medicines for Malaria Venture
- Luuk Berning
- TropIQ Health Sciences
- Judith M. Bolscher
- TropIQ Health Sciences
- Claudia Demarta-Gatsi
- Medicines for Malaria Venture
- Rob W. M. Henderson
- TropIQ Health Sciences
- Tonnie Huijs
- TropIQ Health Sciences
- Karin M. J. Koolen
- TropIQ Health Sciences
- Patrick K. Tumwebaze
- Infectious Diseases Research Collaboration
- Tomas Yeo
- Department of Microbiology & Immunology, Columbia University Irving Medical Center
- Anna C. C. Aguiar
- Sao Carlos Institute of Physics, University of São Paulo, São Carlos, São Paulo, Brazil
- Iñigo Angulo-Barturen
- The Art of Discovery
- Alisje Churchyard
- Department of Life Sciences, Imperial College London
- Jake Baum
- Department of Life Sciences, Imperial College London
- Benigno Crespo Fernández
- Global Health, GlaxoSmithKline
- Aline Fuchs
- Medicines for Malaria Venture
- Francisco-Javier Gamo
- Global Health, GlaxoSmithKline
- Rafael V. C. Guido
- Sao Carlos Institute of Physics, University of São Paulo, São Carlos, São Paulo, Brazil
- María Belén Jiménez-Diaz
- The Art of Discovery
- Dhelio B. Pereira
- Research Center for Tropical Medicine of Rondonia
- Rosemary Rochford
- Department of Immunology and Microbiology, University of Colorado Anschutz School of Medicine
- Camille Roesch
- Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge
- Laura M. Sanz
- Global Health, GlaxoSmithKline
- Graham Trevitt
- Sygnature Discovery
- Benoit Witkowski
- Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge
- Sergio Wittlin
- Swiss Tropical and Public Health Institute
- Roland A. Cooper
- Department of Natural Sciences and Mathematics, Dominican University of California
- Philip J. Rosenthal
- Department of Medicine, University of California
- Robert W. Sauerwein
- Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center
- Joost Schalkwijk
- Department of Dermatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center
- Pedro H. H. Hermkens
- Hermkens Pharma Consultancy
- Roger V. Bonnert
- Medicines for Malaria Venture
- Brice Campo
- Medicines for Malaria Venture
- David A. Fidock
- Department of Microbiology & Immunology, Columbia University Irving Medical Center
- Manuel Llinás
- Department of Chemistry and Huck Center for Malaria Research, The Pennsylvania State University
- Jacquin C. Niles
- Department of Biological Engineering, Massachusetts Institute of Technology
- Taco W. A. Kooij
- Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center
- Koen J. Dechering
- TropIQ Health Sciences
- DOI
- https://doi.org/10.1038/s41467-022-29688-5
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 16
Abstract
Here, de Vries et al. perform a pre-clinical characterization of the antimalarial compound MMV693183: the compound targets acetyl-CoA synthetase, has efficacy in humanized mice against Plasmodium falciparum infection, blocks transmission to mosquito vectors, is safe in rats, and pharmacokinetic-pharmacodynamic modeling informs about a potential oral human dosing regimen.
