Activity of compounds 30–47 in two influenza virus cell–based assays
| Compound | Influenza virusa vRNP reconstitution assay in HEK293T cells | Virus yield assay in MDCK cellsb | ||||||
|---|---|---|---|---|---|---|---|---|
| Antiviral activity EC50c | Cytotoxicity CC50d | Antiviral activitye Human A/PR/8/34 | Cytotoxicity CC50 | |||||
| Human A/ PR/8/34 | Human B/ Yamanashi | Avian 50-92/ PB2-627E | Avian 50-92/ PB2-627K | EC99 | EC90 | |||
| μM | ||||||||
| 30 | >100 | NDf | ND | ND | >200 | ND | ND | ND |
| 31 | 92 | 59 | >200 | 87 | >200 | 85 | 55 | 126 |
| 32 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 33 | 77 | 18 | 39 | 62 | >200 | >25 | >25 | ≥169 |
| 34 | >100 | ND | ND | ND | >100 | ND | ND | ND |
| 35 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 36 | 16 | 11 | 17 | 12 | >200 | >12.5 | >12.5 | >200 |
| 37 | 48 | 29 | 54 | 30 | >200 | >25 | >25 | ≥184 |
| 38 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 39 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 40 | 166 | 65 | 121 | 121 | >200 | 95 | 69 | ≥194 |
| 41 | 45 | 43 | 96 | 62 | 136 | 64 | 38 | >200 |
| 42 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 43 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 44 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 45 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 46 | >100 | ND | ND | ND | >200 | ND | ND | ND |
| 47 | >100 | ND | ND | ND | >200 | ND | ND | ND |
↵a 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.
↵b HEK293T cells, human embryonic kidney 293T cells; MDCK cells, Madin-Darby canine kidney cells.
↵c EC50, 50% effective concentration (μM), i.e., compound concentration producing 50% reduction in vRNP-driven firefly reporter signal, estimated at 24 hours after transfection.
↵d CC50, 50% cytotoxic concentration (μM) at 24 hours determined by MTS cell viability assay.
↵e 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.
↵f ND, Not done.