在患有各种免疫抑制性疾病的COVID-19患者中对remdesivir耐药性突变的特征
Takaya Ichikawa1, Tomokazu Tamura2, Naganori Nao3
1Department of Hematology, Faculty of Medicine, Hokkaido University, Sapporo, Japan; Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
Antiviral research
|August 30, 2025
概括
在免疫功能低下的患者中,SARS-CoV-2 nsp12基因的突变可能导致雷梅西维尔耐药性. 这些突变,特别是在严重免疫缺陷的个体中,影响病毒生长和药物的有效性.
科学领域:
- 病毒学
- 免疫学
- 药理学
背景情况:
- 免疫功能低下的患者可能会出现长期的病毒感染,并发展抗病毒性.
- 雷梅西维尔 (RDV) 针对SARS-CoV-2RNA聚合酶 (nsp12),但已知与耐药性相关的突变.
- 促进耐药病毒出现的特定宿主免疫因素及其特征尚不清楚.
研究的目的:
- 在免疫功能低下的COVID-19患者中调查与remdesivir耐药性相关的nsp12突变.
- 确定与这些突变相关的病毒学特征和免疫状态.
主要方法:
- 从接受RDV治疗的15名免疫功能低下的COVID-19患者中采集了临床样本.
- 变种分析发现了nsp12基因的突变.
- 在体外分析中使用重组病毒来评估突变对病毒生长和RDV敏感性的影响.
主要成果:
- 在80%的患者中发现了七种nsp12突变 (V792I,M794I,E796D,E796K,C799F,C799Y,T803I),其中M794I和V792I是最常见的.
- 在严重的ICP (血液恶性瘤,移植) 中,突变的发生率高于非严重的ICP (固体癌症,自身免疫性疾病).
- 突变病毒的生长减少,但增加了RDV EC50 (1.8至3.6倍).
结论:
- 严重免疫功能受损的患者更容易发展SARS-CoV-2 nsp12突变,从而产生对remdesivir的耐药性.
- 在严重的ICP中监测这些耐药性突变对于有效的SARS-CoV-2治疗策略至关重要.
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