A Standardized Antiviral Pipeline for Human Norovirus in Human Intestinal Enteroids Demonstrates No Antiviral Activity of Nitazoxanide.
Miranda A LewisNicolás W Cortés-PenfieldKhalil EttayebiKetki PatilGurpreet KaurFrederick H NeillRobert L AtmarSasirekha RamaniMary K EstesPublished in: bioRxiv : the preprint server for biology (2023)
Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis. In immunocompetent hosts, symptoms usually resolve within three days; however, in immunocompromised persons, HuNoV infection can become persistent, debilitating, and sometimes life-threatening. There are no licensed therapeutics for HuNoV due to a near half-century delay in its cultivation. Treatment for chronic HuNoV infection in immunosuppressed patients anecdotally includes nitazoxanide, a broad-spectrum antimicrobial licensed for treatment of parasite-induced gastroenteritis. Despite its off-label use for chronic HuNoV infection, nitazoxanide has not been clearly demonstrated to be an effective treatment. In this study, we established a standardized pipeline for antiviral testing using multiple human small intestinal enteroid (HIE) lines representing different intestinal segments and evaluated whether nitazoxanide inhibits replication of 5 HuNoV strains in vitro . Nitazoxanide did not exhibit high selective antiviral activity against any HuNoV strains tested, indicating it is not an effective antiviral for norovirus infection. HIEs are further demonstrated as a model to serve as a pre-clinical platform to test antivirals against human noroviruses to treat gastrointestinal disease.
Keyphrases
- endothelial cells
- induced pluripotent stem cells
- pluripotent stem cells
- high glucose
- end stage renal disease
- escherichia coli
- liver failure
- chronic kidney disease
- staphylococcus aureus
- small molecule
- ejection fraction
- diabetic rats
- combination therapy
- respiratory failure
- plasmodium falciparum
- single cell
- oxidative stress