TY - JOUR
T1 - One health therapeutics
T2 - Target-Based drug development for cryptosporidiosis and other apicomplexa diseases
AU - Van Voorhis, Wesley C.
AU - Hulverson, Matthew A.
AU - Choi, Ryan
AU - Huang, Wenlin
AU - Arnold, Samuel L.M.
AU - Schaefer, Deborah A.
AU - Betzer, Dana P.
AU - Vidadala, Rama S.R.
AU - Lee, Sangun
AU - Whitman, Grant R.
AU - Barrett, Lynn K.
AU - Maly, Dustin J.
AU - Riggs, Michael W.
AU - Fan, Erkang
AU - Kennedy, Thomas J.
AU - Tzipori, Saul
AU - Doggett, J. Stone
AU - Winzer, Pablo
AU - Anghel, Nicoleta
AU - Imhof, Dennis
AU - Müller, Joachim
AU - Hemphill, Andrew
AU - Ferre, Ignacio
AU - Sanchez-Sanchez, Roberto
AU - Ortega-Mora, Luis Miguel
AU - Ojo, Kayode K.
N1 - Funding Information: The authors would like to acknowledge Drs. Wim Hol, Eric T. Larson, and Ethan Merritt for their structural expertise in solving the CDPK1 structure, scientists at AbbVie Inc. who helped with characterizing safety and PK of BKIs including Drs. Dale J. Kempf, Kennan Marsh, James J. Lynch, and Wayne R. Buck, scientists at PATH who have advised us on drug discovery and particularly Dr. Robert Choy, Dr. Anja Joachim and her group at the University of Vienna, Austria, for their work on C. suis, and Dr. Gema Alvarez-Garcia and her group for the work on besnoitiosis. Funding for these studies was provided by National Institute of Allergy and Infectious Diseases, National Institutes of Health (grant numbers R21AI123690, R01AI089441, R01AI111341, R01A1112427, and R01HD080670), the US Department of Agriculture, National Institute of Food and Agriculture (grant numbers 2014-06183 and 2019-07512; Project #ARZT-5704210-A50-133), and the Swiss National Science Foundation (grant number 310030_1846629), the Bill & Melinda Gates Foundation under award number [OPP ID: OPP1160955], and PATH award # [DFI.1850-02-01291794-SUB; and DFI 1850-02-405099]. J. Stone Doggett received funding from VA Merit Review Award BX004522 from the U.S. Department of Veterans Affairs Biomedical Laboratory Research and Development. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation. Funding Information: The authors would like to acknowledge Drs. Wim Hol, Eric T. Larson, and Ethan Merritt for their structural expertise in solving the CDPK1 structure, scientists at AbbVie Inc. who helped with characterizing safety and PK of BKIs including Drs. Dale J. Kempf, Kennan Marsh, James J. Lynch, and Wayne R. Buck, scientists at PATH who have advised us on drug discovery and particularly Dr. Robert Choy, Dr. Anja Joachim and her group at the University of Vienna, Austria, for their work on C. suis, and Dr. Gema Alvarez-Garcia and her group for the work on besnoitiosis. Funding for these studies was provided by National Institute of Allergy and Infectious Diseases , National Institutes of Health (grant numbers R21AI123690 , R01AI089441 , R01AI111341 , R01A1112427 , and R01HD080670 ), the US Department of Agriculture , National Institute of Food and Agriculture (grant numbers 2014-06183 and 2019-07512 ; Project #ARZT-5704210-A50-133), and the Swiss National Science Foundation (grant number 310030_1846629 ), the Bill & Melinda Gates Foundation under award number [OPP ID: OPP1160955], and PATH award # [DFI.1850-02-01291794-SUB; and DFI 1850-02-405099]. J. Stone Doggett received funding from VA Merit Review Award BX004522 from the U.S. Department of Veterans Affairs Biomedical Laboratory Research and Development . The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation. Publisher Copyright: © 2020
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - Antiparastics
KW - Apicomplexa
KW - Kinase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85098854693&partnerID=8YFLogxK
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U2 - https://doi.org/10.1016/j.vetpar.2020.109336
DO - https://doi.org/10.1016/j.vetpar.2020.109336
M3 - Article
C2 - 33418437
SN - 0304-4017
VL - 289
JO - Veterinary Parasitology
JF - Veterinary Parasitology
M1 - 109336
ER -