Originally developed and commercialized as an antiprotozoal agent,
nitazoxanide was later identified as a first-in-class broad-spectrum
antiviral drug and has been repurposed for the treatment of
influenza. A Phase 2b/3 clinical trial recently published in The Lancet
Infectious Diseases found that
oral administration of
nitazoxanide 600mg twice daily for five days reduced the duration of clinical symptoms and reduced viral shedding compared to placebo in persons with laboratory-confirmed
influenza. The same study also suggested a potential benefit for subjects with
influenza-like illness who did not have
influenza or other documented respiratory
viral infection. From a chemical perspective,
nitazoxanide is the scaffold for a new class of drugs called thiazolides. These small-molecule drugs target host-regulated processes involved in viral replication.
Nitazoxanide is orally bioavailable and safe with extensive post-marketing experience involving more than 75 million adults and children. A new dosage formulation of
nitazoxanide is presently undergoing global Phase 3 clinical development for the treatment of
influenza.
Nitazoxanide inhibits a broad range of
influenza A and B viruses including
influenza A(pH1N1) and the avian A(H7N9) as well as viruses that are resistant to
neuraminidase inhibitors. It is synergistic with
neuraminidase inhibitors, and combination
therapy with
oseltamivir is being studied in humans as part of ongoing Phase 3 clinical development.
Nitazoxanide also inhibits the replication of a broad range of other
RNA and DNA viruses including respiratory syncytial virus,
parainfluenza, coronavirus, rotavirus, norovirus,
hepatitis B,
hepatitis C,
dengue,
yellow fever, Japanese encephalitis virus and human immunodeficiency virus in cell culture assays. Clinical trials have indicated a potential role for thiazolides in treating rotavirus and norovirus
gastroenteritis and
chronic hepatitis B and
chronic hepatitis C. Ongoing and future clinical development is focused on viral
respiratory infections, viral
gastroenteritis and emerging
infections such as
dengue fever.