Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses
Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses
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DOI：
10.1128/aac.45.10.2723-2732.2001
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发表时间：
2001-10-01
影响因子：
4.9
通讯作者：
Webster, RG
中科院分区：
文献类型：
--
作者：
Govorkova, EA;Leneva, IA;Webster, RG
口服神经氨酸酶（NA）抑制剂RWJ-270201与扎那米韦和奥司他韦平行测试，以抑制组织培养中的NA活性和复制。然后测试这些试剂对小鼠抵抗致死性H5 N1和H9 N2病毒感染的保护作用。在体外，RWJ-270201对所有9种NA亚型都非常有效。RWJ-270201（50%抑制浓度，0.9至4.3 nM）的NA抑制上级扎那米韦和奥司他韦羧酸盐。RWJ-270201抑制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 μ M）。每天每公斤体重给予10 mg RWJ-270201的小鼠可完全免受流感A/Hong Kong/156/97（H5 N1）和A/quail/Hong Kong/G1/97（H9 N2）病毒的致命攻击。RWJ-270201和奥司他韦在1.0和10 mg/kg的每日剂量下均显著降低小鼠肺中的病毒滴度，并防止病毒传播至大脑。当暴露于H5 N1病毒后48小时开始治疗时，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至少与扎那米韦或奥司他韦对禽流感病毒一样有效，并且可能具有潜在的临床用途，用于治疗可能从鸟类传播到人类的新出现的流感病毒。
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 muM). 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.