The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to Plasmodium falciparum parasite resistance

Author:

Murithi James M.1ORCID,Pascal Cécile2ORCID,Bath Jade1,Boulenc Xavier3ORCID,Gnädig Nina F.1ORCID,Pasaje Charisse Flerida A.4ORCID,Rubiano Kelly1ORCID,Yeo Tomas1ORCID,Mok Sachel1ORCID,Klieber Sylvie5ORCID,Desert Paul3ORCID,Jiménez-Díaz María Belén6ORCID,Marfurt Jutta7ORCID,Rouillier Mélanie8ORCID,Cherkaoui-Rbati Mohammed H.8ORCID,Gobeau Nathalie8,Wittlin Sergio910,Uhlemann Anne-Catrin11ORCID,Price Ric N.71213ORCID,Wirjanata Grennady7ORCID,Noviyanti Rintis14,Tumwebaze Patrick15,Cooper Roland A.16,Rosenthal Philip J.17ORCID,Sanz Laura M.18,Gamo Francisco Javier18ORCID,Joseph Jayan19ORCID,Singh Shivendra19,Bashyam Sridevi19,Augereau Jean Michel2,Giraud Elie2,Bozec Tanguy2,Vermat Thierry2ORCID,Tuffal Gilles5ORCID,Guillon Jean-Michel2,Menegotto Jérôme2,Sallé Laurent5ORCID,Louit Guillaume20ORCID,Cabanis Marie-José5ORCID,Nicolas Marie Françoise20ORCID,Doubovetzky Michel2,Merino Rita2,Bessila Nadir2ORCID,Angulo-Barturen Iñigo6ORCID,Baud Delphine8,Bebrevska Lidiya8,Escudié Fanny8ORCID,Niles Jacquin C.4ORCID,Blasco Benjamin8ORCID,Campbell Simon8,Courtemanche Gilles21ORCID,Fraisse Laurent2ORCID,Pellet Alain2,Fidock David A.111ORCID,Leroy Didier8ORCID

Affiliation:

1. Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.

2. Sanofi, Infectious Diseases Therapeutic Area, Marcy l’Etoile, France.

3. Sanofi Pasteur, Marcy L’Etoile, France.

4. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

5. Sanofi R&D, Translational Medicine & Early Development, Montpellier, France.

6. The Art of Discovery, Bizkaia, Basque Country, Spain.

7. Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.

8. Medicines for Malaria Venture, Geneva, Switzerland.

9. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.

10. Universität Basel, Basel, Switzerland.

11. Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.

12. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

13. Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

14. Eijkman Institute for Molecular Biology, Jakarta, Indonesia.

15. Infectious Diseases Research Collaboration, Kampala, Uganda.

16. Department of Natural Sciences and Mathematics, Dominican University of California, San Rafael, CA, USA.

17. Department of Medicine, University of California, San Francisco, CA, USA.

18. Global Health Pharma Research Unit, GSK, Tres Cantos, Madrid, Spain.

19. Syngene International Ltd., Bangalore, India.

20. Sanofi, Vitry-sur-Seine, France.

21. Bioaster, Paris, France.

Abstract

We report an acylguanidine preclinical candidate with pharmacological features compatible with single low-dose malaria cure.

Funder

U.S. Department of Defense

National Institute of Allergy and Infectious Diseases

Bill and Melinda Gates Foundation

Human Frontier Science Program

Medicines for Malaria Venture

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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