In Vitro Activity of the Neuraminidase Inhibitor GS4071 Against Influenza Viruses.
- 作者：Hayden ; FG ; Rollins ; BS
- 刊名：Antiviral Research
- 出版年：1997
- 期刊代码：7_01663542
- 类别：imm
- 出版时间：April, 1997
- 卷：34
- 期：2
- 页码：A86
- 文件大小：106 K
摘要
The carbocyclic sialic acid analog GS4071 is a selective inhibitor of influenza virus neuraminidases (NA) and is active in experimental murine influenza after oral administration. We assessed the in vitro activity of GS4071 in comparison to the NA inhibitor GG167 for a range of clinical isolates and laboratory strains of influenza A and B viruses by plaque inhibition assay in Madin Darby canine kidney (MDCK) cell monolayers. We also determined effects on virus yield in explants of human adenoid and in the transformed human bronchial epithelial cell line BEAS-2B. By plaque inhibition assay in MDCK, the 50%inhibitory concentrations (EC50) for GS4071 and GG167 were generally comparable. The median EC50 values for both drugs were 0.1 μg/ml for 18 influenza A/H3N2, >10 μg/ml for 8 A/H1N1, and 0.1 μg/ml for 10 B clinical isolates recovered in cell culture between 1983-96. For egg-grown strains of A/Texas/91(H1N1) and B/Yamagata/88, the EC50s were <0.1 μg/ml for both. For both drugs the EC90 values (≥ 1 log10 reduced yield at 48 hrs) were <0.1 μg/ml for an A/Virginia/95(H3N2) and <0.01 μg/ml for A/Texas/36/91(H1N1) in adenoid explants. The drugs were somewhat less active against the A/Texas strain in BEAS-2B monolayers (EC90, 0.02 μg/ml for GS4071, 0.2 μg/ml for GG167). An A/Singapore/1/57(H2N2) virus selected for resistance in the basis of a hemagglutinin mutation was not inhibited by either drug (EC50 > 10 μg/ml). In contrast, a reassortant A/NWS-G70C virus resistant to GG167 on the basis of a neuraminidase mutation had EC50 values of > 10 μg/ml for GG167 but 0.2 μg/ml for GS4071. GS4071 has potency and antiviral spectrum at least comparable to that of GG167 in vitro and is also active against certain viruses with reduced susceptibility to GG167 on the basis of a neuraminidase mutation.