Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir againstH5N1, H9N2, and other avian influenza viruses

The orally administered neuraminidase (NA) inhibitor RWJ-270201 was tested in parallel with zanamivir and oseltamivir against a panel of avian influen za viruses for inhibition of NA activity and replication in tissue culture. The agents were then tested for protection of mice against lethal H5N1 and H9N2 virus infection. In vitro, RWJ-270201 was highly effective against al l nine NA subtypes. NA inhibition by RWJ-270201 (50% inhibitory concentrati on, 0.9 to 4.3 nM) was superior to that by zanamivir and oseltamivir carbox ylate. RWJ-270201 inhibited the replication of avian influenza viruses of b oth Eurasian and American lineages in MDCK cells (50% effective concentrati on, 0.5 to 11.8 muM). Mice given 10 mg of RWJ-270201 per kg of body weight per day were completely protected against lethal challenge with influenza A /Hong Kong/156/97 (H5N1) and A/quail/Hong Kong/G1/97 (H9N2) viruses. Both R WJ-270201 and oseltamivir significantly reduced virus titers in mouse lungs at daily dosages of 1.0 and 10 mg/kg and prevented the spread of virus to the brain. When treatment began 48 h after exposure to H5N1 virus, 10 mg of RWJ-270201/kg/day protected 50% of mice from death. These results suggest that RWJ-270201 is at least as effective as either zanamivir or oseltamivir against avian influenza viruses and may be of potential clinical use for t reatment of emerging influenza viruses that may be transmitted from birds t o humans.