新型siRNA疗法证明了对SARS-CoV-2的多变体疗效
Ellen Bowden-Reid1, Scott Ledger1, Yuan Zhang1
1Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.
Antiviral research
|July 21, 2023
概括
新型短干扰RNAs (siRNAs) 对包括耐药菌株在内的多种SARS-CoV-2变体表现出强大的广泛抗病毒活性. 这些RNA干扰疗法为COVID-19治疗提供了一个有希望的直接作用的抗病毒选择.
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:
- 严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 导致COVID-19,对新兴变种有效的有限的广谱直接作用抗病毒疗法.
- 免疫功能低下的个体和那些面临严重或长期COVID风险的人需要除了接种疫苗之外的其他治疗选择.
- 短干扰RNA (siRNA) 疗法为具有高抗性基因障碍的广泛抗病毒治疗提供了一个有前途的途径.
研究的目的:
- 开发和评估针对SARS-CoV-1和SARS-CoV-2基因组保存区域的新型siRNA.
- 评估这些siRNAs对各种SARS-CoV-2血统的多变体抗病毒功效.
- 为了比较siRNA疗法与现有的抗病毒药物的疗效,并评估多重siRNA策略.
主要方法:
- 设计和合成针对SARS-CoV-1和SARS-CoV-2高度保守的基因组区域的新型siRNAs.
- 在体外测试siRNA对多种SARS-CoV-2变异的疗效,测量细胞存活率和病毒RNA减少.
- 对siRNA抗病毒活性对Sotrovimab和Remdesivir进行比较分析,并评估多重siRNA的疗效.
主要成果:
- siRNA治疗显示出对病毒介导的细胞死亡 (>97%的细胞存活率) 和减少病毒核体RNA (高达99.9%) 的显著保护.
- 开发的siRNAs对包括Omicron在内的八种SARS-CoV-2血统表现出多变体的抗病毒功效.
- 与Sotrovimab和Remdesivir相比,siRNAs显示出更强大的抗病毒作用,在复合时有效性提高.
结论:
- 针对保存的病毒基因组区域的新型siRNA提供了一种高度有效的广泛的直接作用抗病毒策略,用于对抗多种SARS-CoV-2变异.
- 这些siRNA疗法证明了治疗COVID-19的潜力,包括对当前抗病毒药物和疫苗有抗性变异的感染.
- 多重化siRNA可以进一步增强抗病毒功效,突出其作为多功能治疗平台的潜力.
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