One health therapeutics: Target-Based drug development for cryptosporidiosis and other apicomplexa diseases

Wesley C Van Voorhis; Matthew A Hulverson; Ryan Choi; Wenlin Huang; Samuel L M Arnold; Deborah A Schaefer; Dana P Betzer; Rama S R Vidadala; Sangun Lee; Grant R Whitman; Lynn K Barrett; Dustin J Maly; Michael W Riggs; Erkang Fan; Thomas J Kennedy; Saul Tzipori; J Stone Doggett; Pablo Winzer; Nicoleta Anghel; Dennis Imhof; Joachim Müller; Andrew Hemphill; Ignacio Ferre; Roberto Sanchez-Sanchez; Luis Miguel Ortega-Mora; Kayode K Ojo

doi:10.1016/j.vetpar.2020.109336

One health therapeutics: Target-Based drug development for cryptosporidiosis and other apicomplexa diseases

Vet Parasitol. 2021 Jan:289:109336. doi: 10.1016/j.vetpar.2020.109336. Epub 2020 Dec 15.

Authors

Wesley C Van Voorhis¹, Matthew A Hulverson², Ryan Choi², Wenlin Huang³, Samuel L M Arnold², Deborah A Schaefer⁴, Dana P Betzer⁴, Rama S R Vidadala⁵, Sangun Lee⁶, Grant R Whitman², Lynn K Barrett², Dustin J Maly⁵, Michael W Riggs⁴, Erkang Fan³, Thomas J Kennedy⁷, Saul Tzipori⁶, J Stone Doggett⁸, Pablo Winzer⁹, Nicoleta Anghel⁹, Dennis Imhof⁹, Joachim Müller⁹, Andrew Hemphill⁹, Ignacio Ferre¹⁰, Roberto Sanchez-Sanchez¹⁰, Luis Miguel Ortega-Mora¹⁰, Kayode K Ojo²

Affiliations

¹ Center for Emerging and Re-emerging Infectious Diseases (CERID), Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, 98109, USA. Electronic address: wesley@uw.edu.
² Center for Emerging and Re-emerging Infectious Diseases (CERID), Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, 98109, USA.
³ Department of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
⁴ School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, 85721, USA.
⁵ Department of Chemistry, University of Washington, Seattle, WA, 98195, USA.
⁶ Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, 01536, USA.
⁷ Eleven Bravo LLC, Westport, WI, 53597, USA.
⁸ Oregon Health & Science University, Portland, OR, 97239, USA.
⁹ Institute of Parasitology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, 3012, Bern, Switzerland.
¹⁰ Saluvet, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s/n, 28040, Madrid, Spain.

Abstract

This is a review of the development of bumped-kinase inhibitors (BKIs) for the therapy of One Health parasitic apicomplexan diseases. Many apicomplexan infections are shared between humans and livestock, such as cryptosporidiosis and toxoplasmosis, as well as livestock only diseases such as neosporosis. We have demonstrated proof-of-concept for BKI therapy in livestock models of cryptosporidiosis (newborn calves infected with Cryptosporidium parvum), toxoplasmosis (pregnant sheep infected with Toxoplasma gondii), and neosporosis (pregnant sheep infected with Neospora caninum). We discuss the potential uses of BKIs for the treatment of diseases caused by apicomplexan parasites in animals and humans, and the improvements that need to be made to further develop BKIs.

Keywords: Antiparastics; Apicomplexa; Kinase inhibitors.

Publication types

Review

MeSH terms

Animals
Antiparasitic Agents / pharmacology*
Apicomplexa
Cryptosporidiosis / drug therapy*
Humans
One Health*
Piperidines / pharmacology*
Pyrimidines / pharmacology*
Quinolines / pharmacology*

Substances

Antiparasitic Agents
BKI 1369
Piperidines
Pyrimidines
Quinolines

Abstract

Publication types

MeSH terms

Substances

Grants and funding