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SARS-CoV-2 蛋白药物靶点全景:新药研发的潜在药理学见解。

SARS-CoV-2 protein drug targets landscape: a potential pharmacological insight view for the new drug development.

机构信息

Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Kolkata, West Bengal India.

Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Gangwon-do, Republic of Korea.

出版信息

Expert Rev Clin Pharmacol. 2021 Feb;14(2):225-238. doi: 10.1080/17512433.2021.1874348. Epub 2021 Jan 27.

DOI:10.1080/17512433.2021.1874348
PMID:33423554
Abstract

: Protein drug targets play a significant choice in different stages of the drug discovery process. There is an urgent need to understand the drug discovery approaches and protein drug targets (PDT) of SARS-CoV-2, with structural insights for the development of SARS-CoV-2 drugs through targeted therapeutic approach.: We have described the protein as a drug target class and also discussed various drug discovery approaches for SARS-CoV-2 involving the protein drug targets such as drug repurposing study, designing of viral entry inhibitors, viral replication inhibitors, and different enzymes of the virus. We have performed comprehensive literature search from the popular databases such as PubMed Google scholar, Web of Science, and Scopus. Finally, we have illustrated the structural landscape of different significant viral proteins (3 CLpro or Mpro, PLpro, RdRp, helicase, S protein) and host proteins as drug targets (cathepsin L, furin, TMPRSS2, ACE2).: The structural landscape of PDT with their binding pockets, and significant residues involved in binding has been discussed further to better understand the PDT and the structure-based drug discovery for SARS-CoV-2. This attempt will increase more therapeutic options, and combination therapies with a multi-target strategy.

摘要

蛋白药物靶点在药物发现过程的不同阶段起着重要的选择作用。迫切需要了解 SARS-CoV-2 的药物发现方法和蛋白药物靶点(PDT),通过靶向治疗方法获得 SARS-CoV-2 药物的结构见解。我们将蛋白描述为一个药物靶点类别,并讨论了涉及 SARS-CoV-2 蛋白药物靶点的各种药物发现方法,例如药物再利用研究、病毒进入抑制剂、病毒复制抑制剂和病毒的不同酶的设计。我们从 PubMed、Google Scholar、Web of Science 和 Scopus 等流行数据库中进行了全面的文献检索。最后,我们说明了不同重要病毒蛋白(3CLpro 或 Mpro、PLpro、RdRp、解旋酶、S 蛋白)和宿主蛋白作为药物靶点(组织蛋白酶 L、弗林蛋白酶、TMPRSS2、ACE2)的结构景观。进一步讨论了 PDT 的结构景观及其结合口袋,以及参与结合的重要残基,以便更好地了解 PDT 和 SARS-CoV-2 的基于结构的药物发现。这一尝试将增加更多的治疗选择,并采用多靶点策略的联合治疗。

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