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狐ACE2与不同sarbecoviruses的RBDs的结合和结构基础
Junsen Chen1, Junqing Sun2, Zepeng Xu3
1State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Institute of Medical Virology, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, 430071, China.
狐可以与许多沙贝科病毒结合,包括SARS-CoV-2. SARS-CoV-2 变种中的特定突变可以降低狐的易感性,但狐仍然是各种冠状病毒的潜在宿主.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 动物传播疾病 动物传播疾病
背景情况:
- 众所周知,狐在实验条件下容易感染SARS-CoV-2.
- 在狐种群中报告了SARS-CoV和SARS-CoV-2的自然感染.
- 了解宿主-病原体相互作用对于动物传染病监测至关重要.
研究的目的:
- 调查狐 ангиотензин转化酶2 (ACE2) 与各种萨尔贝科病毒的结合亲和力.
- 阐明沙贝科病毒与狐ACE2结合的结构基础.
- 评估这些相互作用对狐对SARS-CoV-2和相关病毒的敏感性的影响.
主要方法:
- 结合测试用于评估狐ACE2和沙贝科病毒受体结合域 (RBDs) 之间的相互作用.
- 电子显微镜 (cryo-EM) 用于确定狐ACE2的结构,该结构与SARS-CoV,SARS-CoV-2原型和Omicron BF.7.7.的RBD复杂.
- 结构分析以确定控制结合亲和力的关键残留物和相互作用.
主要成果:
- 狐ACE2表现出广泛的结合能力,对多种萨尔贝科病毒的RBD进行结合.
- 低温EM结构揭示了特定的相互作用,包括SARS-CoV RBD (Y498) 和狐ACE2 (K353) 之间的关键子-π相互作用.
- 发现SARS-CoV-2亚变体中的K417突变会削弱对狐ACE2的结合,可能降低易感性.
结论:
- 狐ACE2表现出多功能结合多种类型的萨尔贝科病毒,这表明狐是潜在的储库.
- 结构洞察力突出了特定的相互作用,这些相互作用决定了SARS-CoV和SARS-CoV-2与狐ACE2之间的结合亲和力差异.
- 这些发现强调了对狐持续监测沙贝科病毒的重要性,以减轻动物传播的风险.
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