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与抗SARS-CoV-2药物耐药性相关的突变:选择而不是诱导

Philippe Colson^1,2,3, Jérémy Delerce¹, Pierre Pontarotti^1,4

¹IHU Méditerranée Infection, 19-21 boulevard Jean Moulin, Marseille, France.

Journal of medical virology

|February 16, 2024

概括

在Nirmatrelvir药物上市之前,在SARS-CoV-2的基因组和准物种中发现了耐药性突变. 这些突变,包括E166V,已经存在并且可能影响蛋白酶结构,突出显示了基因组监测的必要性.

科学领域:

病毒学病毒学
基因组学就是基因组学.
结构生物学结构生物学

背景情况:

据报道,严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 对抗蛋白酶尼尔马特里尔维尔的耐药性.
了解这些耐药性突变的患病率和影响对于有效的抗病毒治疗至关重要.

研究的目的:

在2022年1月之前收集的病毒基因组和准物种中检测与nirmatrelvir抗性相关的SARS-CoV-2突变.
分析关键突变 (如E166V) 对3CLpro蛋白酶的结构影响.

主要方法:

从呼吸道样本 (2020-2023) 中对62,673个SARS-CoV-2基因组和准物种数据进行生物信息分析.
使用Python对38种特定的3CLpro-nirmatrelvir耐药性突变进行查.
使用瑞士Pdb查看器和莫莱格罗分子查看器使用E166V突变的SARS-CoV-2蛋白酶的结构建模.

主要成果:

在417个 (0.67%) 分析的基因组中检测到22个 (58%) 的向耐药突变,主要来自2020-2021年的样本.
在22种检测到的突变中,12种突变中发现了APOBEC签名.
在病毒类准物种中发现了15种耐尼马特雷尔维尔抗性突变的少数读物,包括E166V.
预计E166V突变对3CLpro结构的影响有限,但可能会阻碍药物结合.

结论:

在药物广泛使用之前,SARS-CoV-2种群中存在对尼马特里尔维尔耐药性的突变.
这些发现强调了持续基因组监测和SARS-CoV-2准物种的表征的重要性,以监测抗病毒耐药性.
以前存在的抗药性突变可能会影响涅马特里尔维尔治疗的疗效,需要仔细监测.

关键词:

这就是SARS-CoV-2病毒.基因组是基因组的组成部分.突变是发生在突变中的突变.尼尔马特里尔维尔是什么意思准物种类型准物种类型电阻的电阻是指电阻的电阻选择的选择选择的选择.

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