Table 1

Susceptibility of influenza A (H1N1) viruses to T-705 and NA inhibitors before and after serial passage in MDCK cells in the presence and absence of T-705

H1N1 virusPassageT-705 presentSusceptibility (mean ± SD) to:
T-705 (EC50 [μM])aNA inhibitor (IC50 [nM])b
Oseltamivir carboxylateZanamivir
Seasonal viruses
    A/Brisbane/59/20070No17.05 ± 0.710.58 ± 0.000.38 ± 0.02
23No17.28 ± 0.780.55 ± 0.090.37 ± 0.04
23Yes17.82 ± 0.270.51 ± 0.030.37 ± 0.00
    A/New Jersey/15/20070No15.07 ± 0.14296.85 ± 8.410.44 ± 0.00
23No12.50 ± 0.69309.60 ± 6.160.49 ± 0.02
23Yes12.95 ± 0.73319.75 ± 0.350.32 ± 0.04
2009 Pandemic viruses
    A/Denmark/524/20090No15.54 ± 0.560.42 ± 0.010.23 ± 0.03
3No14.76 ± 0.100.40 ± 0.010.28 ± 0.01
3YesNDcNDND
    A/Denmark/528/20090No11.36 ± 0.84172.30 ± 3.110.33 ± 0.01
3No10.53 ± 0.73186.10 ± 3.130.38 ± 0.00
3YesNDNDND
  • a The concentration of T-705 required to protect 50% of MDCK cells (EC50) was determined by plotting the percentage of inhibition of cytotoxicity as a function of T-705 concentration and calculating values from the inhibitor-response curve by using GraphPad Prism 5 software. Values reflect three independent experiments.

  • b The concentration required to inhibit 50% of NA enzymatic activity (IC50) as determined by using MUNANA substrate (100 μM final concentration). Values reflect three independent experiments.

  • c ND, not determined due to low virus infectivity. The limit of detection was 1.0 log10 PFU/ml.