抑制TMEM16蛋白质的药物阻断SARS-CoV-2尖端诱导的结合体
Luca Braga1, Hashim Ali1, Ilaria Secco1
1King's College London, British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine & Sciences, London, UK.
Nature
|April 7, 2021
概括
研究人员发现,SARS-CoV-2尖端蛋白会导致肺细胞融合,形成结合体. 尼克洛萨米德药物有效地抑制了这种融合,这表明它有可能通过向这种特定机制来治疗COVID-19.
科学领域:
- 病毒学
- 细胞生物学
- 药物发现
背景情况:
- COVID-19 具有独特的症状,如肺血栓和炎症.
- 导致这些COVID-19特征的潜在病理尚不完全理解.
- COVID-19 患者感染的肺细胞表现出异常的形态和多核化,形成结合细胞.
研究的目的:
- 调查COVID-19症状的病理基质.
- 确定由SARS-CoV-2尖端蛋白介导的合成细胞形成的抑制剂.
- 探索现有的COVID-19药物的潜在治疗用途.
主要方法:
- 对3000多种已批准的药物进行高含量显微镜查.
- 评估药物在抑制尖端介导细胞融合 (突触形成) 的有效性.
- 评估药物对病毒复制和细胞病变的有效性.
主要成果:
- 发现了83种抑制细胞融合的药物.
- 尼克洛萨米德在阻断突形成方面表现出显著的有效性.
- 尼克洛萨米德抑制了振荡和TMEM16F活动.
结论:
- 由SARS-CoV-2尖端蛋白激活引起的结合细胞形成是COVID-19的一个关键病理机制.
- 尼克洛萨米德通过向TMEM16F离子通道有效地抑制合成细胞的形成.
- 重新使用尼克洛萨米德可能为COVID-19治疗提供一种新的治疗策略.
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