In vitro and in vivo activities of T-705 and oseltamivir against influenza virus

Antivir Chem Chemother. 2003 Sep;14(5):235-41. doi: 10.1177/095632020301400502.

Abstract

T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has a potent and selective inhibitory activity against influenza virus. We studied the effects of an infectious dose on the anti-influenza virus activities of T-705 and oseltamivir, a commercially available neuraminidase inhibitor, both in vitro and in vivo. Plaque formation of influenza A/PR/8/34 virus was completely inhibited by 10 microg/ml of T-705 after 72 h incubation, whereas visible plaque formation was detected in the plate treated with GS 4071, the active form of oseltamivir (10 microg/ml). The antiviral activity of T-705 was not influenced by an increase in multiplicity of infection (MOI) from 0.0001 to 1, but that of GS 4071 was influenced in a yield reduction assay. No increase in viral yield was seen in either culture supernatant or cells after removal of T-705 (10 microg/ml) but, in contrast, productive infection recurred in culture supernatant and in cells after removal of GS 4071. In mice infected with a high challenge dose of influenza A/PR/8/34 virus, orally administered T-705 (200 and 400 mg/kg/day) completely prevented the death of mice and the survival rates of mice were significantly higher than those in mice treated with oseltamivir (P<0.01). When the treatment was delayed at 1, 13 and 25 h post infection, oral administration of 200 mg/kg of T-705 significantly prevented the death of mice (P<0.01), and the survival rates of mice treated with T-705 were comparable to those of mice treated with oseltamivir. These results suggest that T-705 has the potential to be a potent inhibitor of human influenza virus infections.

Publication types

  • Comparative Study

MeSH terms

  • Acetamides / administration & dosage
  • Acetamides / pharmacology
  • Acetamides / therapeutic use
  • Amides / administration & dosage
  • Amides / pharmacology
  • Amides / therapeutic use
  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use*
  • Drug Evaluation, Preclinical
  • Influenza A virus / drug effects*
  • Influenza A virus / growth & development
  • Mice
  • Orthomyxoviridae Infections / drug therapy*
  • Orthomyxoviridae Infections / mortality
  • Orthomyxoviridae Infections / prevention & control
  • Oseltamivir
  • Pyrazines / administration & dosage
  • Pyrazines / pharmacology
  • Pyrazines / therapeutic use
  • Survival Rate
  • Time Factors

Substances

  • Acetamides
  • Amides
  • Antiviral Agents
  • Pyrazines
  • Oseltamivir
  • favipiravir