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蝙蝠SARS类冠状病毒由弹性酶和TMPRSS2协同激活尖端蛋白

Yuichiro Yamamoto¹, Tetsuya Inoue¹, Naoto Sugiyama¹

¹Laboratory of Molecular Targeted Therapy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 6-3-1, Niijuku, Katsushika-ku, Tokyo, 125-8585, Japan.

Scientific reports

|July 21, 2025

概括

某些蝙蝠冠状病毒,如RaTG13和Khosta-2,如果用弹性酶治疗,可以感染人类细胞. 这种蛋白酶治疗克服了自然障碍,这表明这些严重急性呼吸系统综合征 (SARS) 相关病毒的动物感染风险可能会增加.

科学领域:

病毒学病毒学
分子生物学分子生物学
传染性疾病传染性疾病

背景情况:

在蝙蝠中存在许多sarbecoviruses,但由于宿主限制,大多数不能感染人类细胞.
蛋白酶敏感性是限制冠状病毒动物性感染的关键障碍.

研究的目的:

调查外源蛋白酶治疗是否可以克服与SARS相关的蝙蝠冠状病毒的宿主限制.
确定尖端蛋白分裂在病毒入口和感染性中的作用.

主要方法:

使用了表达RaTG13和Khosta-2尖端蛋白的伪型病毒.
用各种蛋白酶 (elastase,trypsin,thermolysin) 处理的VeroE6/TMPRSS2细胞.
评估病毒进入,感染性和尖端蛋白分裂,包括TMPRSS2抑制的影响和特定的尖端蛋白突变.

主要成果:

弹性酶治疗促进了RaTG13和Khosta-2伪型病毒通过ACE2介导进入细胞.
弹性酶通过增加尖端蛋白分裂和融合性来增强传染性,依赖于TMPRSS2.2.
素和热解没有影响;一种特定的突变 (S809D) 损害了弹性酶诱导的感染力.

结论:

尖端蛋白的蛋白质分解处理是 RaTG13 和 Khosta-2 感染的限制.
弹性酶可以克服这种限制,增强病毒的进入和感染力.
在炎症组织中分泌的弹性酶可能会增加sarbecoviruses的动物感染潜力.

关键词:

蝙蝠是一种类似SARS的冠状病毒.弹性酶 (Elastase) 是一种可靠的药物.霍斯塔-2号是第二个.在 RaTG13 中,尖蛋白质是一种尖蛋白质.

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