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Updated: Jan 10, 2026

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一个SARS-CoV-2 Mpro突变赋予恩西特雷尔维尔耐药性,矛盾地增加了涅马特雷尔维尔易感性
Seong Cheol Min1, Jin-Ju Seo2, Ju Hwan Jeong1,3
1Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Chungbuk, Republic of Korea.
Nature communications
|November 22, 2025
概括
在SARS-CoV-2 3CL蛋白酶 (Mpro) 中的一种新型突变赋予了对恩西特里尔维尔的耐药性,但增加了对涅马特里尔维尔的敏感性. 这一发现支持治疗耐药COVID-19感染的替代抗病毒策略.
科学领域:
- 病毒学 病毒学
- 药物耐药性 药物耐药性 药物耐药性
- 结构生物学 结构生物学
背景情况:
- 抗病毒药物耐药的SARS-CoV-2变种构成重大威胁,特别是对高风险个体.
- 尼马特里尔维尔和恩西特里尔维尔向病毒3CL蛋白酶 (Mpro),但它们的抗药性概况不同.
研究的目的:
- 调查Mpro中特定突变对尼马特里尔维尔和恩西特里尔维尔敏感性的影响.
- 探索差异性耐药性配置文件的治疗影响.
主要方法:
- 在Mpro.中识别和表征一种甘氨酸23删除 (Δ23G) 突变.
- 在体外敏感性测定和雄性仓鼠感染模型.
- 对Mpro突变及其对抑制剂结合的影响的结构分析.
主要成果:
- 该Mpro-Δ23G突变赋予了对恩西特里尔维尔 (约35倍) 的高水平耐药性,并增加了对涅马特里尔维尔 (约8倍) 的敏感性.
- 与Mpro-Δ23G重组病毒的复制,致病性和传染性降低,部分通过T45I突变恢复.
- 结构分析揭示了影响抑制剂结合选择性的结构变化.
结论:
- Mpro 抑制剂的不同耐药性概况突出显示了尼尔马特里尔维尔和恩西特里尔维尔的顺序或替代使用的潜力.
- 这项研究提供了关于在SARS-CoV-2感染中管理抗病毒耐药性的见解.
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