ArticleAntimicrobial agents and chemotherapy2018
Nitazoxanide Inhibits Human Norovirus Replication and Synergizes with Ribavirin by Activation of Cellular Antiviral Response.
Article in Antimicrobial agents and chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- The Effect of Nitazoxanide on the Clinical Outcomes in Patients with COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Clinical drug investigation · 2022Pooled it
- Organoids Gone Viral: A Comprehensive Review on Human Organoid Models to Study Viral Pathogenesis.Viruses · 2026Review
- Toxic agranulocytosis following nitazoxanide treatment for norovirus diarrhea in a kidney transplant recipient: A case report and review of literature.World journal of transplantation · 2025Article
- Chronic persistent Norovirus in the immune-compromised host.Current opinion in infectious diseases · 2025Review
- CVID Enteropathy Associated With Chronic Norovirus Infection: Background, Clinical Features, and Therapeutic Aspects.Reviews in medical virology · 2025Review
- Human norovirus cultivation systems and their use in antiviral research.Journal of virology · 2024Review
- Favipiravir induces HuNoV viral mutagenesis and infectivity loss with clinical improvement in immunocompromised patients.Clinical immunology (Orlando, Fla.) · 2024Article
- Gastrointestinal tract organoids as novel tools in drug discovery.Frontiers in pharmacology · 2024Review
- Standardization of an antiviral pipeline for human norovirus in human intestinal enteroids demonstrates nitazoxanide has no to weak antiviral activity.Antimicrobial agents and chemotherapy · 2023Article
- Therapeutic potential of salicylamide derivatives for combating viral infections.Medicinal research reviews · 2023Review
- A Standardized Antiviral Pipeline for Human Norovirus in Human Intestinal Enteroids Demonstrates No Antiviral Activity of Nitazoxanide.bioRxiv : the preprint server for biology · 2023Article
- On-target inhibition of Cryptosporidium parvum by nitazoxanide (NTZ) and paclitaxel (PTX) validated using a novel MDR1-transgenic host cell model and algorithms to quantify the effect on the parasite target.PLoS neglected tropical diseases · 2023Article
- Human Norovirus Efficiently Replicates in Differentiated 3D-Human Intestinal Enteroids.Journal of virology · 2022Article
- Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency.The Journal of infectious diseases · 2022Article
- Nitazoxanide and COVID-19: A review.Molecular biology reports · 2022Review
- Article
- An Open Label, Adaptive, Phase 1 Trial of High-Dose Oral Nitazoxanide in Healthy Volunteers: An Antiviral Candidate for SARS-CoV-2.Clinical pharmacology and therapeutics · 2022Article
- Norovirus in Cancer Patients: A Review.Open forum infectious diseases · 2021Review
- Dose prediction for repurposing nitazoxanide in SARS-CoV-2 treatment or chemoprophylaxis.British journal of clinical pharmacology · 2021Article
- Experimental Pharmacotherapy for COVID-19: The Latest Advances.Journal of experimental pharmacology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Norovirus is the main cause of viral gastroenteritis worldwide. Although norovirus gastroenteritis is self-limiting in immunocompetent individuals, chronic infections with debilitating and life-threatening complications occur in immunocompromised patients. Nitazoxanide (NTZ) has been used empirically in the clinic and has demonstrated effectiveness against norovirus gastroenteritis. In this study, we aimed at uncovering the antiviral potential and mechanisms of action of NTZ and its active metabolite, tizoxanide (TIZ), using a human norovirus (HuNV) replicon. NTZ and TIZ, collectively referred to as thiazolides (TZD), potently inhibited replication of HuNV and a norovirus surrogate, feline calicivirus. Mechanistic studies revealed that TZD activated cellular antiviral response and stimulated the expression of a subset of interferon-stimulated genes (ISGs), particularly interferon regulatory factor 1 (IRF-1), not only in a Huh7 cell-based HuNV replicon, but also in naive Huh7 and Caco-2 cells and novel human intestinal organoids. Overexpression of exogenous IRF-1 inhibited HuNV replication, whereas knockdown of IRF-1 largely attenuated the antiviral activity of TZD, suggesting that IRF-1 mediated TZD inhibition of HuNV. By using a Janus kinase (JAK) inhibitor, CP-690550, and a STAT1 knockout approach, we found that TZD induced antiviral response independently of the classical JAK-signal transducers and activators of transcription (JAK-STAT) pathway. Furthermore, TZD and ribavirin synergized to inhibit HuNV replication and completely depleted the replicons from host cells after long-term treatment. In summary, our results demonstrated that TZD combated HuNV replication through activation of cellular antiviral response, in particular by inducing a prominent antiviral effector, IRF-1. NTZ monotherapy or combination with ribavirin represent promising options for treating norovirus gastroenteritis, especially in immunocompromised patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.