组胺受体H1作为SARS-CoV-2的替代受体起作用
Fei Yu1, Xiaoqing Liu2,3, Hailan Ou1
1Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
mBio
|July 2, 2024
概括
组胺受体H1 (HRH1) 作为另一种SARS-CoV-2受体,增强了ACE2-依赖性进入. 针对HRH1的抗胰岛素药物阻断病毒感染,显示出对COVID-19的治疗潜力.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 使用宿主因素,如人类血管素转化酶2 (hACE2) 进入.
- 抗组胺药物,特别是组胺受体H1 (HRH1) 抗剂,已经显示出对SARS-CoV-2感染的强烈抑制.
研究的目的:
- 研究HRH1作为SARS-CoV-2受体的作用.
- 阐明HRH1促进病毒进入的机制.
- 评估HRH1抗体对抗SARS-CoV-2的治疗潜力.
主要方法:
- 在HRH1和SARS-CoV-2尖端蛋白之间进行直接结合测试.
- 同免疫沉以评估HRH1与haCE2的相互作用.
- 使用各种SARS-CoV-2突变体和抗组胺药物的抑制试验.
- 真正的SARS-CoV-2感染测定和人性化的小鼠挑战实验.
主要成果:
- HRH1直接与SARS-CoV-2尖端蛋白结合,作为替代受体.
- HRH1通过与 hACE2的相互作用,协同增强了依赖于 hACE2的病毒入口.
- 抗胰岛素药物通过阻断尖端蛋白-HRH1相互作用,有效地抑制SARS-CoV-2感染,平均IC50为2.4μM对各种突变.
- 预防作用在体内得到证实,证明了治疗潜力.
结论:
- HRH1作为SARS-CoV-2的替代受体,并增强了HACE2介导的进入.
- 针对HRH1的抗组胺药物代表了对抗冠状病毒病19 (COVID-19) 的可行的治疗策略.
- 重用抗组胺剂为COVID-19治疗提供了一个有希望的途径.
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