赫辛通过ACE2向机制抑制SARS-CoV-2Omicron和变种伪病毒感染
Rafael Zúñiga1, Whitney Venturini2, Natalia González1
1Laboratorio de Fisiología Molecular, Facultad de Medicina, Universidad de Talca, Talca, Chile.
Frontiers in pharmacology
|January 28, 2026
概括
赫素化通过破坏尖峰-hACE2相互作用,有效地抑制SARS-CoV-2感染. 这种药物显示出治疗COVID-19及其变体的潜力.
科学领域:
- 病毒学 病毒学
- 药物发现 药物发现 药物发现
- 分子生物学分子生物学
背景情况:
- 严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 导致COVID-19,一种高度传染性呼吸系统疾病.
- 该病毒通过与人类血管酶转化酶2 (hACE2) 结合的尖端糖蛋白 (S蛋白) 感染宿主细胞.
- 破坏S蛋白的受体结合域 (RBD) 和HACE2之间的高亲和相互作用可以降低病毒感染力.
研究的目的:
- 评估赫辛化在抑制SARS-CoV-2感染方面的疗效.
- 调查赫辛对抗SARS-CoV-2变种的作用机制.
主要方法:
- 使用了一种表达 hACE2 (HEK-293/ACE2) 和Omicron变种伪病毒的稳定HEK-293细胞系.
- 通过光或光酶活性在用赫辛治疗的细胞中评估感染水平.
- 采用了免疫光,西部斑点,细胞毒性测试,计算对接和分子动力学模拟.
主要成果:
- 勃罗姆赫西因显著抑制了SARS-CoV-2 Omicron变种感染,其IC50为17.3 ± 0.9μM.
- 观察到大约40%的抑制对阿尔法,贝塔和三角形变种在40μM.
- 分子模拟表明,赫辛在关键相互作用位点附近与 hACE2 结合 (Phe40,Phe390,Asn394).
结论:
- 赫辛通过破坏SARS-CoV-2尖峰-hACE2接口的稳定性,作为一种进入抑制剂.
- 赫素化是一种潜在的重用药物候选者,用于针对当前和新出现的SARS-CoV-2变种的治疗策略.
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