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当前对新型冠状病毒-19 的分子药物靶点和新兴治疗策略的认识。

Current understanding on molecular drug targets and emerging treatment strategy for novel coronavirus-19.

机构信息

Neuroscience Division, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.

Department of Pharmaceutics, ISF College of Pharmacy, Moga, 142001, Punjab, India.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2021 Jul;394(7):1383-1402. doi: 10.1007/s00210-021-02091-5. Epub 2021 May 7.

DOI:10.1007/s00210-021-02091-5
PMID:33961065
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8102151/
Abstract

SARS-CoV-2 is an enveloped positive-sense RNA virus, contain crown-like spikes on its surface, exceptional of large RNA genome, and a special replication machinery. Common symptoms of SARS-CoV-2 include cough, common cold, fever, sore throat, and a variety of severe acute respiratory disease (SARD) such as pneumonia. SARS-CoV-2 infects epithelial cells, T-cells, macrophages, and dendritic cells and also influences the production and implantation of pro-inflammatory cytokines and chemokines. Repurposing of various drugs during this emergency condition can reduce the rate of mortality as well as time and cost. Two druggable protein and enzyme targets have been selected in this review article due to their crucial role in the viral life cycle. The eukaryotic translation initiation factor (eIF4A), cyclophilin, nucleocapsid protein, spike protein, Angiotensin-converting enzyme 2 (ACE2), 3-chymotrypsin-like cysteine protease (3CLpro), and RNA-dependent RNA polymerase (RdRp) play significant role in early and late phase of SARS-CoV-2 replication and translation. This review paper is based on the rationale of inhibiting of various SARS-CoV-2 proteins and enzymes as novel therapeutic approaches for the management and treatment of patients with SARS-CoV-2 infection. We also discussed the structural and functional relationship of different proteins and enzymes to develop therapeutic approaches for novel coronavirus SARS-CoV-2.

摘要

SARS-CoV-2 是一种包膜的正链 RNA 病毒,在其表面有冠状样突起,除了大型 RNA 基因组外,还有一种特殊的复制机制。SARS-CoV-2 的常见症状包括咳嗽、普通感冒、发热、喉咙痛以及各种严重急性呼吸道疾病(SARD),如肺炎。SARS-CoV-2 感染上皮细胞、T 细胞、巨噬细胞和树突状细胞,也会影响促炎细胞因子和趋化因子的产生和植入。在这种紧急情况下,重新利用各种药物可以降低死亡率以及时间和成本。由于在病毒生命周期中起着至关重要的作用,本文选择了两种可成药的蛋白和酶靶标。真核翻译起始因子(eIF4A)、亲环素、核衣壳蛋白、刺突蛋白、血管紧张素转换酶 2(ACE2)、3-糜蛋白酶样半胱氨酸蛋白酶(3CLpro)和 RNA 依赖性 RNA 聚合酶(RdRp)在 SARS-CoV-2 复制和翻译的早期和晚期都发挥着重要作用。本文基于抑制各种 SARS-CoV-2 蛋白和酶的基本原理,为管理和治疗 SARS-CoV-2 感染患者提供了新的治疗方法。我们还讨论了不同蛋白和酶的结构和功能关系,以开发针对新型冠状病毒 SARS-CoV-2 的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33d/8102151/854e80b659e9/210_2021_2091_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33d/8102151/efac27680bbf/210_2021_2091_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33d/8102151/3ef8f857d4a5/210_2021_2091_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33d/8102151/072f9e3a91b2/210_2021_2091_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33d/8102151/3fcc42fea4f3/210_2021_2091_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33d/8102151/fe554842e1ee/210_2021_2091_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33d/8102151/854e80b659e9/210_2021_2091_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33d/8102151/efac27680bbf/210_2021_2091_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33d/8102151/3ef8f857d4a5/210_2021_2091_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33d/8102151/072f9e3a91b2/210_2021_2091_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33d/8102151/3fcc42fea4f3/210_2021_2091_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33d/8102151/fe554842e1ee/210_2021_2091_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a33d/8102151/854e80b659e9/210_2021_2091_Fig6_HTML.jpg

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