核糖体失活蛋白MAP30和Momordin可以抑制SARS-CoV-2病毒
Norman R Watts1, Elif Eren1, Ira Palmer1
1Protein Expression Laboratory, NIAMS, NIH, Bethesda, Maryland, United States of America.
PloS one
|June 29, 2023
概括
苦瓜蛋白MAP30和Momordin有效地抑制了SARS-CoV-2在肺细胞中的复制. 它们的RNA N-glycosylase活性对于这种抗病毒效应至关重要,有可能为新的治疗策略提供潜力.
科学领域:
- 生物化学 生物化学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 新出现的SARS-CoV-2变种需要新的抗病毒点.
- 苦瓜中的核糖体无活化蛋白 (RIPs),如MAP30和Momordin,表现出广泛的抗病毒活性.
- MAP30已经证明了强大的HIV-1抑制与低细胞毒性.
研究的目的:
- 为了评估MAP30和Momordin对SARS-CoV-2复制的疗效.
- 调查这些RIP的作用机制和结构-活动关系.
- 探索与其他化合物的潜在协同效应.
主要方法:
- 在体外测试中使用A549人类肺细胞来确定IC50和CC50值.
- 在MAP30 (Y70,K171,K215) 中关键残留物的位点定向突变发生.
- 评估病毒抑制和细胞毒性,有或没有细胞透和其他药物.
主要成果:
- MAP30和Momordin强烈抑制了SARS-CoV-2复制 (IC50~0.2μM) 的发生,细胞毒性低 (CC50~2μM).
- 泰洛辛70的突变消除了抗病毒活性和细胞毒性,证实了RNA N-糖酶的参与.
- 氨酸171和215的突变降低了细胞毒性,但也降低了病毒抑制.
- 细胞透没有改变蛋白质活性;没有观察到与甲或甲的协同作用.
结论:
- MAP30和Momordin是强大的SARS-CoV-2抑制剂,通过它们的RNA N-糖酶活性起作用.
- 结构上的差异并不妨碍两种RIP之间具有相似的抗病毒功效.
- 这些蛋白质代表了开发新的SARS-CoV-2治疗方法的有希望的候选人.
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