Govorkova E A, Leneva I A, Goloubeva O G, Bush K, Webster R G
Department of Virology and Molecular Biology, St. Jude's Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
Antimicrob Agents Chemother. 2001 Oct;45(10):2723-32. doi: 10.1128/AAC.45.10.2723-2732.2001.
The orally administered neuraminidase (NA) inhibitor RWJ-270201 was tested in parallel with zanamivir and oseltamivir against a panel of avian influenza viruses for inhibition of NA activity and replication in tissue culture. The agents were then tested for protection of mice against lethal H5N1 and H9N2 virus infection. In vitro, RWJ-270201 was highly effective against all nine NA subtypes. NA inhibition by RWJ-270201 (50% inhibitory concentration, 0.9 to 4.3 nM) was superior to that by zanamivir and oseltamivir carboxylate. RWJ-270201 inhibited the replication of avian influenza viruses of both Eurasian and American lineages in MDCK cells (50% effective concentration, 0.5 to 11.8 microM). Mice given 10 mg of RWJ-270201 per kg of body weight per day were completely protected against lethal challenge with influenza A/Hong Kong/156/97 (H5N1) and A/quail/Hong Kong/G1/97 (H9N2) viruses. Both RWJ-270201 and oseltamivir significantly reduced virus titers in mouse lungs at daily dosages of 1.0 and 10 mg/kg and prevented the spread of virus to the brain. When treatment began 48 h after exposure to H5N1 virus, 10 mg of RWJ-270201/kg/day protected 50% of mice from death. These results suggest that RWJ-270201 is at least as effective as either zanamivir or oseltamivir against avian influenza viruses and may be of potential clinical use for treatment of emerging influenza viruses that may be transmitted from birds to humans.
口服神经氨酸酶（NA）抑制剂RWJ - 270201与扎那米韦和奥司他韦同时针对一组禽流感病毒进行了测试，以检测其对NA活性的抑制作用以及在组织培养中的复制抑制情况。然后测试了这些药物对小鼠抵抗致死性H5N1和H9N2病毒感染的保护作用。在体外，RWJ - 270201对所有九种NA亚型均具有高效性。RWJ - 270201的NA抑制作用（50%抑制浓度，0.9至4.3 nM）优于扎那米韦和奥司他韦羧酸盐。RWJ - 270201抑制了欧亚和美洲谱系的禽流感病毒在MDCK细胞中的复制（50%有效浓度，0.5至11.8 microM）。每天每千克体重给予10 mg RWJ - 270201的小鼠完全受到保护，免受甲型流感病毒/香港/156/97（H5N1）和甲型流感病毒/鹌鹑/香港/G1/97（H9N2）致死性攻击。RWJ - 270201和奥司他韦在每日剂量为1.0和10 mg/kg时均显著降低了小鼠肺中的病毒滴度，并防止病毒扩散至脑部。当在接触H5N1病毒48小时后开始治疗时，10 mg RWJ - 270201/kg/天可保护50%的小鼠免于死亡。这些结果表明，RWJ - 270201在对抗禽流感病毒方面至少与扎那米韦或奥司他韦一样有效，并且可能在临床上用于治疗可能从鸟类传播给人类的新型流感病毒。
