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通过群体测序揭示的对NITD008耐药的肠道病毒71型（EV71）变异株的突变图谱。

Mutational landscapes of NITD008-resistant EV71 variants revealed through population sequencing.

作者信息

Yu Fang, Zhang Qiu-Yan, Zhang Zhe-Rui, Deng Cheng-Lin, Zhang Bo

机构信息

State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China; University of Chinese Academy of Sciences, Beijing, 100049, China.

State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.

出版信息

Virol Sin. 2025 Jun;40(3):503-505. doi: 10.1016/j.virs.2025.05.003. Epub 2025 May 21.

DOI:10.1016/j.virs.2025.05.003
PMID:40409380
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12282453/
Abstract

• The mutation spectra between WT population and NITD008-resistant populations during replication are compared. • The 2C protein may be a new target of NITD008 as a nucleotide analogue against EV71 infection. • Antiviral effect of NITD008 against EV71 is associated with increased frequency of U-to-A and U-to-C mutations.

摘要

• 比较野生型群体和NITD008抗性群体在复制过程中的突变谱。

• 2C蛋白可能作为一种核苷酸类似物成为NITD008抗EV71感染的新靶点。

• NITD008对EV71的抗病毒作用与U-to-A和U-to-C突变频率增加有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16a0/12282453/648caa0166f7/figs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16a0/12282453/35b44f4e6053/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16a0/12282453/432cb191f1a1/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16a0/12282453/5ab3a5af56cc/figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16a0/12282453/648caa0166f7/figs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16a0/12282453/35b44f4e6053/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16a0/12282453/432cb191f1a1/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16a0/12282453/5ab3a5af56cc/figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16a0/12282453/648caa0166f7/figs3.jpg

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本文引用的文献

1
Antiviral Peptides Targeting the Helicase Activity of Enterovirus Nonstructural Protein 2C.靶向肠道病毒非结构蛋白 2C 解旋酶活性的抗病毒肽。
J Virol. 2021 May 24;95(12). doi: 10.1128/JVI.02324-20.
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The Structure, Function, and Mechanisms of Action of Enterovirus Non-structural Protein 2C.肠道病毒非结构蛋白2C的结构、功能及作用机制
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An upstream protein-coding region in enteroviruses modulates virus infection in gut epithelial cells.
肠道病毒中的上游蛋白编码区调节肠道上皮细胞中的病毒感染。
Nat Microbiol. 2019 Feb;4(2):280-292. doi: 10.1038/s41564-018-0297-1. Epub 2018 Nov 26.
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Viral Polymerase-Helicase Complexes Regulate Replication Fidelity To Overcome Intracellular Nucleotide Depletion.病毒聚合酶-解旋酶复合物调节复制保真度以克服细胞内核苷酸耗竭。
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Human Enterovirus Nonstructural Protein 2CATPase Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone.人肠道病毒非结构蛋白2CATP酶兼具RNA解旋酶和ATP非依赖性RNA伴侣的功能。
PLoS Pathog. 2015 Jul 28;11(7):e1005067. doi: 10.1371/journal.ppat.1005067. eCollection 2015 Jul.
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Deep sequencing analysis of viral infection and evolution allows rapid and detailed characterization of viral mutant spectrum.病毒感染与进化的深度测序分析能够快速且详细地表征病毒突变谱。
Bioinformatics. 2015 Jul 1;31(13):2141-50. doi: 10.1093/bioinformatics/btv101. Epub 2015 Feb 19.
7
Inhibition of enterovirus 71 by adenosine analog NITD008.腺苷类似物NITD008对肠道病毒71型的抑制作用
J Virol. 2014 Oct;88(20):11915-23. doi: 10.1128/JVI.01207-14. Epub 2014 Aug 6.
8
Alphavirus mutator variants present host-specific defects and attenuation in mammalian and insect models.甲病毒突变体变体在哺乳动物和昆虫模型中表现出宿主特异性缺陷和减毒。
PLoS Pathog. 2014 Jan;10(1):e1003877. doi: 10.1371/journal.ppat.1003877. Epub 2014 Jan 16.
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Coronaviruses lacking exoribonuclease activity are susceptible to lethal mutagenesis: evidence for proofreading and potential therapeutics.缺乏外切核酸酶活性的冠状病毒易发生致死性突变：校正证据和潜在治疗方法。
PLoS Pathog. 2013 Aug;9(8):e1003565. doi: 10.1371/journal.ppat.1003565. Epub 2013 Aug 15.
10
Patterns of polymorphism and divergence in the VP1 gene of enterovirus 71 circulating in the Asia-Pacific region between 1994 and 2013.1994 年至 2013 年间亚太地区流行的肠道病毒 71 型 VP1 基因的多态性和分化模式。
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