Octaarginine Improves the Efficacy of Nitazoxanide against Cryptosporidium parvum

Abstract

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.

Nano copper-organic framework as a delivery system to improve the efficiency of commercially available drugs for cryptosporidiosis: In vivo experimental study

“…Consequently, there is a critical need for novel effective medications [28,29] . Consequently, Octaarginine proved to improve NTZ efficacy as an anti-cryptosporidial therapeutic [30] . In the current investigation, experimental mice infected with Cryptosporidium were treated for the first time with Antinal and Septrin, either alone or added to Cu-BTC.…”

Bioactive Peptides against Human Apicomplexan Parasites

“…However, the coupling of the peptide octarginine and the antibiotic nitazoxanide showed excellent results, lowering the IC 50 value to 2.9 nM compared to the IC 50 of nitozoanide alone, which was 197 nM. Of all the peptides evaluated, this combination showed the best results [ 86 ].…”

Investigation of the prophylactic and therapeutic effectiveness of oral thyme extract in rats experimentally infected with cryptosporidium parvum

“…In animals, azithromycin, nitazoxanide, paromomycin, halofuginone lactate, tylosin, and decoquinate are some active substances that may be partially effective (Shahiduzzaman and Daugschies 2012 ; Yasa Duru et al 2013 ; Yagci et al 2017 ). Considering the limited efficacy of the agents used for both humans and animals, their failure in eradication, and their toxic effects, there is an urgent need for new, effective, and safe anticryptosporidial agents (Nguyen-Ho-Bao et al 2022 ; Su et al 2022 ).…”