SARS-CoV-2的三角形和欧米克朗变种抵御了人类呼吸道素样蛋白酶的尖裂变
Wenyan Ren1, Weiqi Hong1, Jingyun Yang1
1Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
The Journal of clinical investigation
|September 17, 2024
概括
一种新发现的人类呼吸道素样蛋白酶 (HAT) 通过切割尖蛋白有效降低了SARS-CoV-2的感染力. 然而,Delta和Omicron变异中的突变导致对HAT的耐药性.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 生物化学 生物化学
背景情况:
- 上呼吸道中的可溶性宿主因子对于防御SARS-CoV-2至关重要.
- 了解这些因素可以揭示新的治疗点.
研究的目的:
- 识别和描述具有针对SARS-CoV-2的抗病毒活性的可溶性宿主因子.
- 调查已识别的因素的作用机制和局限性.
主要方法:
- 人类呼吸道素样蛋白酶 (HAT) 的识别和功能测定.
- 在体外和体外小鼠模型中进行SARS-CoV-2感染性测定.
- 对尖端糖蛋白分裂和变异性耐药性的分析.
主要成果:
- 鉴定出HAT是一种蛋白酶,可以在R682切割SARS-CoV-2尖端蛋白,抑制病毒附着和细胞融合.
- 在体内,HAT降低了祖先的SARS-CoV-2感染力.
- 由于在分裂部位附近的P681R/H突变,HAT对Delta和Omicron变种 (BQ.1.1,XBB.1.5) 显示无效.
结论:
- HAT是一种新型的可溶性防御因子,可以对抗祖先的SARS-CoV-2.
- 在SARS-CoV-2变种的尖端蛋白中的突变赋予了对HAT活性的抵抗力.
- 针对当前变种,HAT的有效性有限,这凸显了适应性抗病毒策略的必要性.
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