Table 1.
Inhibitory effect of R-125489, zanamivir, and oseltamivir carboxylate on the NA activity of H5N1 influenza viruses.
Figure 1.
Therapeutic efficacy of CS-8958 and oseltamivir phosphate against H5N1 influenza viruses in mice.
Ten mice per group were intranasally infected with 4 MLD50 of HN30408cl7 (A) or Ind3006 (B). The infected mice were given CS-8958 intranasally or oseltamivir phosphate orally at the indicated doses 2 h post-infection (pi) or twice daily for 5 days beginning 2 h pi. Control mice received saline and water 2 h pi. Survival was monitored daily for 21 days. P values were calculated by a log-rank test using a joint ranking method. Asterisk, P<0.05.
Table 2.
Virus titers in H5N1 virus-infected mice subsequently treated with drug.
Figure 2.
Therapeutic efficacy of CS-8958 and oseltamivir phosphate against oseltamivir-resistant H5N1 influenza viruses in mice.
Eight mice per group were intranasally infected with 4 MLD50 of wild-type VN1203 (A), VN1203-H274Y (B), or VN1203-N294S (C). The infected mice were given CS-8958 intranasally or oseltamivir phosphate orally at the indicated doses 2 h post-infection (pi) or twice daily for 5 days beginning 2 h pi. Control mice received saline and water 2 h pi. Survival was monitored daily for 21 days. P values were calculated by a log-rank test using a joint ranking method. Asterisk, P<0.05.
Figure 3.
Prophylactic effect of CS-8958 and oseltamivir phosphate against H5N1 influenza viruses in mice.
Eight mice per group were given CS-8958 intranasally or oseltamivir phosphate orally at the indicated doses on day 7 (A), 3 (B) or 1 (C) before or 2 h (D) after infection with 4 MLD50 of HN30408cl7. Control mice received saline and water 2 h post-infection. Survival was monitored daily for 21 days. P values were calculated by a log-rank test using a joint ranking method. Asterisk, P<0.05.
Table 3.
Prophylactic efficacy of CS-8958 as measured by H5N1 virus growth in mice.
Figure 4.
Binding stability of NA inhibitors to viruses.
The NA activity of A/New Caledonia/20/99 (H1N1; A), A/Panama/2007/99 (H3N2; B), and B/Mie/1/93 (C) untreated [NA inhibitor (-)] or treated with excess R-125489, peramivir, zanamivir, or oseltamivir carboxylate, was monitored every 15 min for 6 h.