TABLE 5.
Activity of compounds 1–29 in two influenza virus cell–based assays
Data shown are the mean ± S.E.M. of at least three independent tests.
| Compound |
Influenza virusa vRNP reconstitution assay in HEK293T cellsb |
Virus yield assay in MDCK cellsb |
||||||
|---|---|---|---|---|---|---|---|---|
| Antiviral activity
EC50c |
Cytotoxicity CC50d | Human A/PR/8/34
antiviral activitye
|
Cytotoxicity CC50 | |||||
| Human A/PR/8/34 | Human B/Yamanashi | Avian 50-92/ PB2-627E | Avian 50-92/ PB2-627K | EC99 | EC90 | |||
| μM | ||||||||
| 1 | 3.6 | 3.1 | 4.6 | 11 | ≥104 | 8.4 | 5.4 | 181 |
| 2 | 2.8 | 6.9 | 8.5 | 20 | ≥102 | 6.0 | 3.9 | >100 |
| 3 | 1.8 | 0.8 | 6.6 | 17 | ≥103 | 2.9 | 2.0 | >100 |
| 4 | 2.3 | 0.4 | 7.6 | 15 | ≥93 | 5.6 | 3.8 | >100 |
| 5 | 1.7 | 4.4 | 3.9 | 8.8 | ≥106 | 1.5 | 1.0 | >100 |
| 6 | 2.3 | 11 | 7.2 | 15 | ≥94 | 2.7 | 1.9 | >100 |
| 7 | >100 | NDf | ND | ND | >200 | ND | ND | ND |
| 8 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 9 | 57 | 25 | 105 | 29 | 117 | >100 | >100 | >200 |
| 10 | 84 | 116 | 88 | 95 | >200 | 74 | 58 | >200 |
| 11 | 132 | 49 | 47 | 65 | >200 | >100 | ≥90 | ≥184 |
| 12 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 13 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 14 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 15 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 16 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 17 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 18 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 19 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 20 | 72 | 97 | 32 | 37 | >200 | 79 | 55 | ≥194 |
| 21 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 22 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 23 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 24 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 25 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 26 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 27 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 28 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 29 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| Ribavirin | 16 | 3.1 | 50 | 45 | >200 | 10 | 6.7 | >200 |
Reconstituted vRNP complexes from: human influenza A virus, strain A/PR/8/34; human influenza B virus, strain B/Yamanashi/166/98; and avian influenza A virus, strain A/turkey/England/50-92/1991 with a PB2-627E or PB2-627K residue.
HEK293T cells, human embryonic kidney 293T cells; MDCK cells, Madin-Darby canine kidney cells.
EC50, 50% effective concentration (μM), i.e., compound concentration producing 50% reduction in vRNP-driven firefly reporter signal, estimated at 24 hours after transfection.
CC50, 50% cytotoxic concentration (μM) at 24 hours determined by MTS cell viability assay.
Compound concentration (μM) causing a 1-log10 (EC90) or 2-log10 (EC99) reduction in virus yield at 24 hours postinfection, as determined by real-time RT-PCR.
ND, Not done.