Nitazoxanide in the treatment of viral gastroenteritis: a randomized double‐blind placebo‐controlled clinical trial

Rossignol, Jean‐François; El-Gohary, Y.

doi:10.1111/j.1365-2036.2006.03128.x

Cited by 174 publications

(146 citation statements)

References 25 publications

Supporting

Mentioning

142

Contrasting

Order By: Relevance

“…Nitazoxanide (NTZ) is a thiazolide antiinfective with activity against a broad range of anaerobic bacteria, protozoa, and viruses (3,6,9,10). While NTZ was originally developed as a treatment for intestinal protozoan infections, its antiviral properties were discovered during the course of its development for treating cryptosporidiosis in patients with AIDS.…”

mentioning

confidence: 99%

Potential for Hepatitis C Virus Resistance to Nitazoxanide or Tizoxanide

Korba

Elazar

Lui

et al. 2008

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Nitazoxanide and its primary metabolite, tizoxanide, inhibit hepatitis C virus (HCV) replication in HCV replicon systems. To study the potential for resistance, we subjected Huh7 cells harboring HCV replicons to serial passage in 250 M G418 and increasing concentrations of nitazoxanide or tizoxanide. Passage of the replicon-containing cell lines in either compound resulted in increases in the 50% effective concentrations (EC 50 s) (7-to 13-fold), EC 90 s (14-to 36-fold), and 50% cytotoxic concentrations (2-to 4-fold) of both compounds. Serial passage in either compound did not alter the susceptibility of HCV replicons to ribavirin or 2-C-methylcytidine. Interestingly, serial passage in nitazoxanide or tizoxanide resulted in increased sensitivity to alpha interferon 2b: EC 50 s and EC 90 s were reduced three-and eightfold, respectively. Replicons isolated from these cell lines had no greater ability to confer tizoxanide resistance, or increased susceptibility to alpha interferon, than replicons isolated from the parental cell line that had not previously been exposed to nitazoxanide or tizoxanide. These findings are indicative of a cell-mediated activity differing from that of other anti-HCV drugs but complementary with interferon and are consistent with the enhanced response rates observed clinically when nitazoxanide is combined with pegylated interferon therapy. Finally, unlike data for other compounds in advanced clinical development for HCV, these data are consistent with resistance in HCV replicon-containing cell lines conferred by changes in the host and not by mutations in the virus.Nitazoxanide (NTZ) is a thiazolide antiinfective with activity against a broad range of anaerobic bacteria, protozoa, and viruses (3, 6, 9, 10). While NTZ was originally developed as a treatment for intestinal protozoan infections, its antiviral properties were discovered during the course of its development for treating cryptosporidiosis in patients with AIDS. NTZ is undergoing clinical development for the treatment of chronic hepatitis C and has shown promising results as adjunct therapy with peginterferon or peginterferon plus ribavirin (RBV) in treating patients with chronic infections with hepatitis C virus (HCV) genotype 4 (8).NTZ and its circulating metabolite, tizoxanide (TIZ), inhibit the replication of HCV in HCV genotype 1a-and 1b-derived replicon cells. Median 50% effective concentrations (EC 50 s) of approximately 0.13 and 0.15 M for NTZ and TIZ, respectively, were found in these replicon systems (4). NTZ and TIZ exhibit synergistic activity with alpha interferon and 2Ј-Cmethylcytidine (2ЈC-MeC) and are effective against HCV replicons that are resistant to 2ЈC-MeC and telaprevir (VX-950) (4). Furthermore, lead-in treatment of replicon-containing cells with NTZ potentiates the effect of subsequent combination treatment with NTZ plus alpha interferon (4). Antiviral mechanisms are under investigation, but the broad antiviral spectrum of TIZ is consistent with activity on host processes.In this report, we present resu...

show abstract

mentioning

confidence: 99%

Potential for Hepatitis C Virus Resistance to Nitazoxanide or Tizoxanide

Korba

Elazar

Lui

et al. 2008

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…End point studied was the time from first dose of the drug to resolution of symptoms and was significantly low in children who received a 3 day course of nitazoxanide compared to those who received placebo. The same investigator had also done an analogous study in 50 adult patients with similar results [3].…”

Section: Sirmentioning

confidence: 73%

Nitazoxanide use in Rota Viral Diarrhea. Cure or Controversy?

Babu

Chandrasekaran

2010

Indian J Pediatr

View full text Add to dashboard Cite

“…Clinical studies on Nitazoxanide (NTZ), a prototype, for the treatment of chronic hepatitis C, have shown that all responders had low levels of serum HCV RNA (7). Thiazolide derivatives have been shown to be effective against many unicellular organisms and viruses (23,24). Thiazolide derivatives were initially developed for the treatment of intestinal infections.…”

Section: Discussionmentioning

confidence: 99%

Calculation of Wiener Indices of Thiazolides: The Potent Inhibitors of Hepatitis B Virus and Hepatitis C Virus Replication

et al. 2018

View full text Add to dashboard Cite

Background: Hepatitis C Virus is the leading cause of death in liver-related diseases globally. The identification of innovative drug targets and inexpensive therapeutic agents remain a high priority for chronic HCV infection management. In the last few decades, the availability of highly effective interferon-free regimens for HCV treatment is the only possible option for cure of the large number of chronic HCV patients. Direct acting antiviral drugs, such as Sovaldi, are expensive and their efficacy varies from genotype to genotype. In addition, these drugs are advised in combination with ribavirin and interferon, which makes the treatment costly. Thiazolide derivatives are recently emerging antiviral agents that may change current and future therapies for liver complications caused by HBV and HCV. Nitazoxanides are synthetic nitrothiazolyl-salicylamide derivative of thiazolide, which have been used as anti-HCV drugs. The derivatives of thiazolides were randomly screened for anti-HCV and anti-HBV activity in a biological system, yet the stability and other properties of these compounds were not tested. Representing chemical compounds with Hosoya-polynomial produces closed forms of many topological indices, which correlate with the chemical properties of the material under investigation. These indices are used in the development of quantitative structure-activity relationships (QSARs), in which the biological activity and other properties of molecules like boiling point, stability, strain energy, radius of gyration, and viscosity are correlated with their structures.In this paper, Hosoya-polynomials and Weiner indices of some derivatives of thiazolides were determined. Graphs of Hosoya polynomial for these derivatives were also plotted. Objectives: In this study, therefore, it was attempted to extend the research to check the stability and other properties of thiazolide derivatives using the Hosoya-polynomial and Wiener index. Methods: In the first step, Hosoya polynomials of some famous classes of thiazolides were computed, followed by computation of F Wiener indices of thiazolide derivatives. Distance-based graph invariants were used as a structure-descriptor for predicting various physicochemical properties of organic compounds. The Weiner index of 8 derivatives of thiazolidines was computed, including Tizoxanide, and Nitazoxanide. Results: These indices indicate the physiochemical properties of these compounds in relation to stability in the given biological environment. The Wiener indices of the studied compounds ranged from 374 to 684. Out of 8 analyzed compounds, 3 showed Wiener indices of 374. RM-4863 had a maximum index value of 684. Graphs were also drawn for Hosoya polynomials of all these thiazole derivatives. Conclusions:The results confirmed that RM-4863 is a stable physiochemical compound, which might be used as an effective drug for treating viral infections, including HCV and HBV.

show abstract

Nitazoxanide in the treatment of viral gastroenteritis: a randomized double‐blind placebo‐controlled clinical trial

Abstract: SUMMARY BackgroundEnteric viruses including noroviruses and rotavirus are leading causes of diarrhoeal disease and gastroenteritis worldwide, and there is no effective treatment.

Cited by 174 publications

References 25 publications

Potential for Hepatitis C Virus Resistance to Nitazoxanide or Tizoxanide

Potential for Hepatitis C Virus Resistance to Nitazoxanide or Tizoxanide

Nitazoxanide use in Rota Viral Diarrhea. Cure or Controversy?

Calculation of Wiener Indices of Thiazolides: The Potent Inhibitors of Hepatitis B Virus and Hepatitis C Virus Replication

Contact Info

Product

Resources

About