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新兴的 SARS-CoV-2 抗病毒策略:从解析病毒蛋白结构功能到疫苗、抗体和小分子药物的开发。

Newly Emerged Antiviral Strategies for SARS-CoV-2: From Deciphering Viral Protein Structural Function to the Development of Vaccines, Antibodies, and Small Molecules.

机构信息

Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65212, USA.

Department of Surgery, University of Missouri, Columbia, MO 65211, USA.

出版信息

Int J Mol Sci. 2022 May 29;23(11):6083. doi: 10.3390/ijms23116083.


DOI:10.3390/ijms23116083
PMID:35682761
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9181103/
Abstract

Coronavirus disease 2019 (COVID-19) caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the most severe health crisis, causing extraordinary economic disruption worldwide. SARS-CoV-2 is a single-stranded RNA-enveloped virus. The process of viral replication and particle packaging is finished in host cells. Viral proteins, including both structural and nonstructural proteins, play important roles in the viral life cycle, which also provides the targets of treatment. Therefore, a better understanding of the structural function of virus proteins is crucial to speed up the development of vaccines and therapeutic strategies. Currently, the structure and function of proteins encoded by the SARS-CoV-2 genome are reviewed by several studies. However, most of them are based on the analysis of SARS-CoV-1 particles, lacking a systematic review update for SARS-CoV-2. Here, we specifically focus on the structure and function of proteins encoded by SARS-CoV-2. Viral proteins that contribute to COVID-19 infection and disease pathogenesis are reviewed according to the most recent research findings. The structure-function correlation of viral proteins provides a fundamental rationale for vaccine development and targeted therapy. Then, current antiviral vaccines are updated, such as inactive viral vaccines and protein-based vaccines and DNA, mRNA, and circular RNA vaccines. A summary of other therapeutic options is also reviewed, including monoclonal antibodies such as a cross-neutralizer antibody, a constructed cobinding antibody, a dual functional monoclonal antibody, an antibody cocktail, and an engineered bispecific antibody, as well as peptide-based inhibitors, chemical compounds, and clustered regularly interspaced short palindromic repeats (CRISPR) exploration. Overall, viral proteins and their functions provide the basis for targeted therapy and vaccine development.

摘要

新型冠状病毒病 2019(COVID-19)是由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)感染引起的,已成为最严重的卫生危机,在全球范围内造成了非同寻常的经济破坏。SARS-CoV-2 是一种单链 RNA 包膜病毒。病毒复制和颗粒包装过程在宿主细胞中完成。病毒蛋白,包括结构蛋白和非结构蛋白,在病毒生命周期中发挥着重要作用,也为治疗提供了靶点。因此,更好地了解病毒蛋白的结构功能对于加快疫苗和治疗策略的开发至关重要。目前,有几项研究对 SARS-CoV-2 基因组编码的蛋白质的结构和功能进行了综述。然而,大多数研究都是基于对 SARS-CoV-1 颗粒的分析,缺乏对 SARS-CoV-2 的系统综述更新。在这里,我们特别关注 SARS-CoV-2 编码的蛋白质的结构和功能。根据最近的研究结果,综述了有助于 COVID-19 感染和疾病发病机制的病毒蛋白。病毒蛋白的结构-功能相关性为疫苗开发和靶向治疗提供了基本依据。然后,更新了当前的抗病毒疫苗,例如失活病毒疫苗和基于蛋白质的疫苗以及 DNA、mRNA 和环状 RNA 疫苗。还综述了其他治疗选择,包括中和抗体、构建的共结合抗体、双功能单克隆抗体、抗体鸡尾酒和工程化双特异性抗体等单克隆抗体,以及肽基抑制剂、化学化合物和成簇规则间隔短回文重复序列(CRISPR)探索。总体而言,病毒蛋白及其功能为靶向治疗和疫苗开发提供了基础。

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[3]
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[4]
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[5]
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[6]
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[7]
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J Transl Med. 2023-2-25

[8]
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Int J Mol Sci. 2022-12-10

[9]
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本文引用的文献

[1]
Engineering SARS-CoV-2 specific cocktail antibodies into a bispecific format improves neutralizing potency and breadth.

Nat Commun. 2022-9-22

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Cell Rep. 2022-5-17

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Cell. 2022-5-12

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N Engl J Med. 2022-6-9

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Antiviral Res. 2022-2

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