桑吉瓦米辛被SARS-CoV-2聚合酶优先纳入病毒RNA
Ryan P Bennett1, Yasemin Yoluç2, Jason D Salter1
1OyaGen, Inc., Rochester, NY, USA.
Antiviral research
|September 10, 2023
概括
桑吉瓦米辛 (S) 通过将其纳入病毒RNA,有效地抑制SARS-CoV-2. 这种结合不会增加病毒突变率,这表明一种新的抗病毒机制对抗病毒.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 桑吉瓦米辛 (S) 是一种腺类比物,在体外已证明对SARS-CoV-2的抗病毒活性.
- 之前的研究表明,对各种病毒菌株和细胞类型的纳米分子疗效较低.
研究的目的:
- 为了研究sangivamycin在SARS-CoV-2RNA中的结合.
- 为了确定sangivamycin的结合是否会影响病毒突变率.
- 为了阐明sangivamycin抗病毒活性的机制.
主要方法:
- 质谱法 (MS) 用于分析感染细胞和病毒的SARS-CoV-2RNA,以检测sangivamycin的结合.
- 宿主mRNA被净化并分析血胺含量.
- 桑格维三酸盐 (STP) 通过复合SARS-CoV-2RNA依赖RNA聚合酶 (RdRp) 在体外合成并测试RNA结合.
主要成果:
- 观察到桑吉瓦米辛在SARS-CoV-2RNA中的剂量依赖性结合 (每1000个核酸中高达1.8S).
- 加入桑吉瓦米辛并没有改变病毒突变率.
- 宿主mRNA显示的sangivamycin结合是最小的或没有的.
- 实验室试验证实,桑吉瓦米不是链终结剂,并且被SARS-CoV-2 RdRp作为腺 (A) 纳入.
结论:
- 在SARS-CoV-2 RdRp中,圣维三酸盐被纳入病毒RNA中.
- 桑吉瓦米辛的结合不会显著影响病毒RNA合成或突变率.
- 桑吉瓦米对SARS-CoV-2的精确抗病毒机制需要进一步调查.
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