Table 3.
Effects of 2’-deoxy-2’-fluorocytidine and 2’-deoxy-2’, 2’-difluorocytidine on the reolication of influenza viruses in MDCK cells.
| Visul Assay | Neutral Red Uptake Assay | VYR Assaya |
|||||||
|---|---|---|---|---|---|---|---|---|---|
| Influenza Virus |
Virus Subtype | Compound (µM) | IC50b | CC50c | Sld | IC50 | CC50 | SI | IC90e |
| H1N1 | A/CA/07/2009 | 2’-deoxy-2’-fluorocytidine | 3.2 | >100 | >31 | 4.1 | >100 | >24 | 4.6 |
| 2’-deoxy-2’, 2’-difluorocytidine | 0.18 | 2.1 | 11.7 | 0.16 | 1.1 | 6.9 | 0.13 | ||
| H1N1 | A/Hong Kong/2369/2009Rf | 2’-deoxy-2’-fluorocytidine | 2.1 | >100 | >48 | 7 .8 | >100 | >12.8 | 6.3 |
| 2’-deoxy-2’, 2’-difluorocytidine | 0.05 | >100 | >200 | 0.054 | >100 | >1900 | 0.03 | ||
| H3N2 | A//Sydney/05/97 | 2’-deoxy-2’-fluorocytidine | 0.59 | >100 | >170 | 2.5 | >100 | >40 | 6.7 |
| 2’-deoxy-2’, 2’-difluorocytidine | 0.18 | 12 | 67 | 1.2 | 6.8 | 5.7 | 1.6 | ||
| H3N2 | A/Brisbane/10/2007 | 2’-deoxy-2’-fluorocytidine | 1.0 | >100 | >100 | 14 | >100 | >7.1 | 6.8 |
| 2’-deoxy-2’, 2’-difluorocytidine | 0.13 | 5.6 | 43 | 0.16 | 1.3 | 8.1 | 0.14 | ||
| H1N1 X | A/Hong Kong/213/2003H | 2’-deoxy-2’-fluorocytidine | 1.3 | >100 | >77 | 7.2 | >100 | >14 | 5.1 |
| H5N1g | 2’-deoxy-2’, 2’-difluorocytidine | <0.032 | >100 | >3100 | 0.065 | >100 | >1538 | 0.04 | |
| H1N1 X | A/Vietnam/1203/2004 H | 2’-deoxy-2’-fluorocytidine | 2.1 | >100 | >48 | 3.4 | >100 | >29 | 2.9 |
| H5N1 | 2’-deoxy-2’, 2’-difluorocytidine | <0.32 | 320 | >1000 | <0.32 | 160 | >500 | 0.32 | |
| H5N1 | A/Vietnam/1203/2004 | 2’-deoxy-2’-fluorocytidine | 1.4 | >100 | >71 | <0.032 | 26 | >81 | 1.2 |
| 2’-deoxy-2’, 2’-difluorocytidine | <0.032 | >100 | >3100 | <0.032 | >100 | >3100 | 0.03 | ||
| H5N1 | A/Gull/PA/4175/83 | 2’-deoxy-2’-fluorocytidine | 0.91 | >100 | >110 | 1.1 | >100 | >91 | 6.1 |
| 2’-deoxy-2’, 2’-difluorocytidine | 0.21 | >100 | >480 | 0.27 | >100 | 370 | 0.13 | ||
| H5N1 | A/Duck/MN/1525/81 | 2’-deoxy-2’-fluorocytidine | 0.25 | >100 | >400 | 0.21 | >100 | >480 | 5.9 |
| 2’-deoxy-2’, 2’-difluorocytidine | <0.32 | 530 | >1700 | <0.32 | 280 | >880 | 0.25 | ||
| B | Malaysia/2506/2004 | 2’-deoxy-2’-fluorocytidine | 1.9 | >100 | >53 | 4.1 | >100 | >24 | 7.3 |
| 2’-deoxy-2’, 2’-difluorocytidine | <0.032 | >100 | >3100 | 0.068 | >100 | >1500 | 0.11 | ||
| B | Florida/4/2006 | 2’-deoxy-2’-fluorocytidine | 1.0 | >100 | >100 | 1.4 | >100 | >71 | 2.1 |
| 2’-deoxy-2’, 2’-difluorocytidine | <0.32 | 440 | >1400 | <0.32 | 140 | >440 | 1.7 | ||
Values for CPE and NR assays are arithmetic means of three independent experiments. VYR assays were done one time.
a
Virus Yield Reduction Assay;
b
IC50: 50% virus inhibitory concentration;
c
CC50: 50% cell cytotoxic concentration of drug;
d
selective index: Visual and neutral red (NR) SI = CC50/IC50;
e
IC90: 90% virus inhibitory concentration (1log10 drop in virus titer);
f
R= oseltamivir resistant; A/Ann Arbor/6/60 H1N1 virus expressing hemagglutinin and neuraminidase from A/Vietnam/1203/2004 H5N1 virus.