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Octaarginine Improves the Efficacy of Nitazoxanide against Cryptosporidium parvum

Cryptosporidiosis is an intestinal disease that affects a variety of hosts including animals and humans. Since no vaccines exist against the disease till date, drug treatment is the mainstay of disease control. Nitazoxanide (NTZ) is the only FDA-approved drug for the treatment of human cryptosporidi...

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Autores principales: Nguyen-Ho-Bao, Tran, Ambe, Lum A., Berberich, Maxi, Hermosilla, Carlos, Taubert, Anja, Daugschies, Arwid, Kamena, Faustin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227457/
https://www.ncbi.nlm.nih.gov/pubmed/35745507
http://dx.doi.org/10.3390/pathogens11060653
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author Nguyen-Ho-Bao, Tran
Ambe, Lum A.
Berberich, Maxi
Hermosilla, Carlos
Taubert, Anja
Daugschies, Arwid
Kamena, Faustin
author_facet Nguyen-Ho-Bao, Tran
Ambe, Lum A.
Berberich, Maxi
Hermosilla, Carlos
Taubert, Anja
Daugschies, Arwid
Kamena, Faustin
author_sort Nguyen-Ho-Bao, Tran
collection PubMed
description Cryptosporidiosis is an intestinal disease that affects a variety of hosts including animals and humans. Since no vaccines exist against the disease till date, drug treatment is the mainstay of disease control. Nitazoxanide (NTZ) is the only FDA-approved drug for the treatment of human cryptosporidiosis. However, its efficacy in immunocompromised people such as those with AIDS, in malnourished children, or those with concomitant cryptosporidiosis is limited. In the absence of effective drugs against cryptosporidiosis, improving the efficacy of existing drugs may offer an attractive alternative. In the present work, we have assessed the potential of the cell-penetrating peptide (CPP) octaarginine (R8) to increase the uptake of NTZ. Octaarginine (R8) was synthetically attached to NTZ in an enzymatically releasable manner and used to inhibit growth of Cryptosporidium parvum in an in vitro culture system using human ileocecal adenocarcinoma (HCT-8) cell line. We observed a significant concentration-dependent increase in drug efficacy. We conclude that coupling of octaarginine to NTZ is beneficial for drug activity and it represents an attractive strategy to widen the repertoire of anti-cryptosporidial therapeutics. Further investigations such as in vivo studies with the conjugate drug will help to further characterize this strategy for the treatment of cryptosporidiosis.
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spelling pubmed-92274572022-06-25 Octaarginine Improves the Efficacy of Nitazoxanide against Cryptosporidium parvum Nguyen-Ho-Bao, Tran Ambe, Lum A. Berberich, Maxi Hermosilla, Carlos Taubert, Anja Daugschies, Arwid Kamena, Faustin Pathogens Article Cryptosporidiosis is an intestinal disease that affects a variety of hosts including animals and humans. Since no vaccines exist against the disease till date, drug treatment is the mainstay of disease control. Nitazoxanide (NTZ) is the only FDA-approved drug for the treatment of human cryptosporidiosis. However, its efficacy in immunocompromised people such as those with AIDS, in malnourished children, or those with concomitant cryptosporidiosis is limited. In the absence of effective drugs against cryptosporidiosis, improving the efficacy of existing drugs may offer an attractive alternative. In the present work, we have assessed the potential of the cell-penetrating peptide (CPP) octaarginine (R8) to increase the uptake of NTZ. Octaarginine (R8) was synthetically attached to NTZ in an enzymatically releasable manner and used to inhibit growth of Cryptosporidium parvum in an in vitro culture system using human ileocecal adenocarcinoma (HCT-8) cell line. We observed a significant concentration-dependent increase in drug efficacy. We conclude that coupling of octaarginine to NTZ is beneficial for drug activity and it represents an attractive strategy to widen the repertoire of anti-cryptosporidial therapeutics. Further investigations such as in vivo studies with the conjugate drug will help to further characterize this strategy for the treatment of cryptosporidiosis. MDPI 2022-06-06 /pmc/articles/PMC9227457/ /pubmed/35745507 http://dx.doi.org/10.3390/pathogens11060653 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nguyen-Ho-Bao, Tran
Ambe, Lum A.
Berberich, Maxi
Hermosilla, Carlos
Taubert, Anja
Daugschies, Arwid
Kamena, Faustin
Octaarginine Improves the Efficacy of Nitazoxanide against Cryptosporidium parvum
title Octaarginine Improves the Efficacy of Nitazoxanide against Cryptosporidium parvum
title_full Octaarginine Improves the Efficacy of Nitazoxanide against Cryptosporidium parvum
title_fullStr Octaarginine Improves the Efficacy of Nitazoxanide against Cryptosporidium parvum
title_full_unstemmed Octaarginine Improves the Efficacy of Nitazoxanide against Cryptosporidium parvum
title_short Octaarginine Improves the Efficacy of Nitazoxanide against Cryptosporidium parvum
title_sort octaarginine improves the efficacy of nitazoxanide against cryptosporidium parvum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227457/
https://www.ncbi.nlm.nih.gov/pubmed/35745507
http://dx.doi.org/10.3390/pathogens11060653
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