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对抑肽酶在感染非适应性人类流感病毒的小鼠中的抗流感作用的评估。

Evaluation of anti-influenza effects of camostat in mice infected with non-adapted human influenza viruses.

作者信息

Lee M G, Kim K H, Park K Y, Kim J S

机构信息

WHO National Influenza Center, NIH Korea, Seoul, South Korea.

出版信息

Arch Virol. 1996;141(10):1979-89. doi: 10.1007/BF01718208.

DOI:10.1007/BF01718208
PMID:8920829
Abstract

The anti-influenza effects of camostat, a serine protease inhibitor, on in vivo influenza infections were evaluated. Mice which received non-adapted human influenza viruses intranasally, developed a reproducible infection with very low mortality. The infection was readily detected by the recovery of the virus from an oropharyngeal swab. Five-week-old ICR mice received intraperitoneal injections of saline (control), amantadine (known positive drug), or camostat, after infection with influenza A/Taiwan/1/86 virus. Virus detection was performed on day 1, 2, 3, 5, and 7 of postinfection. Both camostat and amantadine were effective in ameliorating mouse influenza. On day 5, mice injected with camostat (45%) or amantadine (50%) showed a lower virus secreting rate than those receiving saline (90%). Additionally, camostat showed strong anti-influenza effects on an amantadine-resistant type A virus and a type B virus infection in vitro. The results show that blocking the hemagglutinin cleavage is an effective target for development of an anti-influenza agent. They also demonstrate that virus detection from the oropharynx of mice, infected with non-adapted virus, is a useful in vivo influenza model.

摘要

评估了丝氨酸蛋白酶抑制剂卡莫司他对体内流感感染的抗流感作用。经鼻内接种未适应的人类流感病毒的小鼠,发生了可重复的感染,死亡率极低。通过从口咽拭子中分离出病毒很容易检测到感染。5周龄的ICR小鼠在感染甲型流感病毒/台湾/1/86后,腹腔注射生理盐水(对照)、金刚烷胺(已知阳性药物)或卡莫司他。在感染后的第1、2、3、5和7天进行病毒检测。卡莫司他和金刚烷胺均能有效改善小鼠流感。在第5天,注射卡莫司他(45%)或金刚烷胺(50%)的小鼠的病毒分泌率低于注射生理盐水的小鼠(90%)。此外,卡莫司他在体外对金刚烷胺耐药的甲型病毒和乙型病毒感染显示出强大的抗流感作用。结果表明,阻断血凝素裂解是开发抗流感药物的有效靶点。它们还证明,从感染未适应病毒的小鼠口咽中检测病毒是一种有用的体内流感模型。

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