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解析并靶向宿主因子以对抗严重急性呼吸综合征冠状病毒2(SARS-CoV-2)和冠状病毒感染:来自CRISPR方法的见解

Deciphering and targeting host factors to counteract SARS-CoV-2 and coronavirus infections: insights from CRISPR approaches.

作者信息

Cui Zhifen, Wang Hongyan, Dong Yizhou, Liu Shan-Lu, Wang Qianben

机构信息

Department of Pathology, Duke University School of Medicine, Durham, NC, United States.

Department of Oncological Sciences, Icahn Genomics Institute, Precision Immunology Institute, Tisch Cancer Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

出版信息

Front Genome Ed. 2023 Jul 13;5:1231656. doi: 10.3389/fgeed.2023.1231656. eCollection 2023.

DOI:10.3389/fgeed.2023.1231656
PMID:37520399
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10372414/
Abstract

Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses depend on host factors for the process of viral infection and replication. A better understanding of the dynamic interplay between viral pathogens and host cells, as well as identifying of virus-host dependencies, offers valuable insights into disease mechanisms and informs the development of effective therapeutic strategies against viral infections. This review delves into the key host factors that facilitate or hinder SARS-CoV-2 infection and replication, as identified by CRISPR/Cas9-based screening platforms. Furthermore, we explore CRISPR/Cas13-based gene therapy strategies aimed at targeting these host factors to inhibit viral infection, with the ultimate goal of eradicating SARS-CoV-2 and preventing and treating related coronaviruses for future outbreaks.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)和其他冠状病毒在病毒感染和复制过程中依赖宿主因子。更好地理解病毒病原体与宿主细胞之间的动态相互作用,以及确定病毒-宿主依赖性,有助于深入了解疾病机制,并为开发有效的抗病毒感染治疗策略提供依据。本综述深入探讨了基于CRISPR/Cas9筛选平台确定的促进或阻碍SARS-CoV-2感染和复制的关键宿主因子。此外,我们探索了旨在靶向这些宿主因子以抑制病毒感染的基于CRISPR/Cas13的基因治疗策略,最终目标是根除SARS-CoV-2,并预防和治疗未来爆发的相关冠状病毒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8da3/10372414/be1009e071c0/fgeed-05-1231656-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8da3/10372414/28378487d47c/fgeed-05-1231656-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8da3/10372414/be1009e071c0/fgeed-05-1231656-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8da3/10372414/28378487d47c/fgeed-05-1231656-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8da3/10372414/be1009e071c0/fgeed-05-1231656-g002.jpg

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本文引用的文献

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Collateral activity of the CRISPR/RfxCas13d system in human cells.CRISPR/RfxCas13d 系统在人类细胞中的非靶向活性。
Commun Biol. 2023 Mar 28;6(1):334. doi: 10.1038/s42003-023-04708-2.
2
The collateral activity of RfxCas13d can induce lethality in a RfxCas13d knock-in mouse model.RfxCas13d 的旁侧活性可诱导 RfxCas13d 敲入小鼠模型的致死性。
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Precise transcript targeting by CRISPR-Csm complexes.CRISPR-Csm 复合物的精确转录靶向。
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Negative autoregulation mitigates collateral RNase activity of repeat-targeting CRISPR-Cas13d in mammalian cells.负向自动调节减轻了重复靶向 CRISPR-Cas13d 在哺乳动物细胞中的 collateral RNase 活性。
Cell Rep. 2022 Aug 16;40(7):111226. doi: 10.1016/j.celrep.2022.111226.
5
Cas13d knockdown of lung protease Ctsl prevents and treats SARS-CoV-2 infection.Cas13d 敲低肺蛋白酶 Ctsl 可预防和治疗 SARS-CoV-2 感染。
Nat Chem Biol. 2022 Oct;18(10):1056-1064. doi: 10.1038/s41589-022-01094-4. Epub 2022 Jul 25.
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Bidirectional genome-wide CRISPR screens reveal host factors regulating SARS-CoV-2, MERS-CoV and seasonal HCoVs.双向全基因组 CRISPR 筛选揭示了宿主调控 SARS-CoV-2、MERS-CoV 和季节性 HCoVs 的因子。
Nat Genet. 2022 Aug;54(8):1090-1102. doi: 10.1038/s41588-022-01110-2. Epub 2022 Jul 25.
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Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection.全基因组双向 CRISPR 筛选鉴定粘蛋白为调节 SARS-CoV-2 感染的宿主因子。
Nat Genet. 2022 Aug;54(8):1078-1089. doi: 10.1038/s41588-022-01131-x. Epub 2022 Jul 25.
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VMP1 and TMEM41B are essential for DMV formation during β-coronavirus infection.VMP1 和 TMEM41B 是β 冠状病毒感染过程中形成 DMV 所必需的。
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9
Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2.全基因组 CRISPR 筛选鉴定 GATA6 为 SARS-CoV-2 的前病毒宿主因子,通过调节 ACE2。
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A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets.全基因组 CRISPR 筛选鉴定出与自噬途径相互作用的蛋白,这些蛋白是保守的冠状病毒靶标。
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