Tizoxanide (Synonyms: NSC 697856)

IC50: 0.17 to 0.21 μM for CIVs

Tizoxanide is the active metabolite of nitazoxanide that is a thiazolide anti-infective drug against anaerobic bacteria, protozoa, and a range of viruses.

Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are major public health problems, causing more than an estimated 500 million chronic infections worldwide. Both HBV and HCV are a source of liver disease, and are the major risk factors for hepatocellular carcinoma.

In vitro: Previous study found that tizoxanide showed potent inhibition of both HBV and HCV replication. Tizoxanide also exhibited selective inhibition of intracellular HBV replication and extracellular virus production by 2.2.15 cells. Tizoxanide could selectively reduce intracellular HCV replication in AVA5 cells. Moreover, the combination of tizoxanide with either recombinant human interferon alpha 2b (IFNα), or an NS5B (HCV polymerase) inhibitor, 2′-C-methyl cytidine, resulted in synergistic interactions against HCV replication. In addition, antiviral activities of tizoxanide against a full-length genotype 1a replicon were equivalent to that observed for AVA5 cells [1].

In vivo: Animal study in an immunosuppressed rat model suggested that relapses were less frequent after treatment with nitazoxanide, the parent drug of tizoxanide, than with the non-absorbable sinefungin and paromomycin [2].

Clinical trial: Nitazoxanide, the parent drug of tizoxanide, is currently in phase II clinical development for treating chronic hepatitis C [1].

References:
[1] Korba BE,Montero AB,Farrar K,Gaye K,Mukerjee S,Ayers MS,Rossignol JF.  Nitazoxanide, tizoxanide and other thiazolides are potent inhibitors of hepatitis B virus and hepatitis C virus replication. Antiviral Res.2008 Jan;77(1):56-63.
[2] Gargala G,Delaunay A,Li X,Brasseur P,Favennec L,Ballet JJ.  Efficacy of nitazoxanide, tizoxanide and tizoxanide glucuronide against Cryptosporidium parvum development in sporozoite-infected HCT-8 enterocytic cells. J Antimicrob Chemother.2000 Jul;46(1):57-60.