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2010 年至 2020 年冠状病毒 3C 样蛋白酶（3CL）抑制剂的发展。

The development of Coronavirus 3C-Like protease (3CL) inhibitors from 2010 to 2020.

机构信息

Faculty of Pharmacy, Shaanxi University of Science & Technology, Xi'an, 710021, PR China.

Faculty of Pharmacy, Shaanxi University of Science & Technology, Xi'an, 710021, PR China.

出版信息

Eur J Med Chem. 2020 Nov 15;206:112711. doi: 10.1016/j.ejmech.2020.112711. Epub 2020 Aug 6.

DOI:10.1016/j.ejmech.2020.112711
PMID:32810751
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7409838/
Abstract

This review fully describes the coronavirus 3CL peptidomimetic inhibitors and nonpeptidic small molecule inhibitors developed from 2010 to 2020. Specifically, the structural characteristics, binding modes and SARs of these 3CL inhibitors are expounded in detail by division into two categories: peptidomimetic inhibitors mainly utilize electrophilic warhead groups to covalently bind the 3CL Cys145 residue and thereby achieve irreversible inhibition effects, whereas nonpeptidic small molecule inhibitors mainly interact with residues in the S1', S1, S2 and S4 pockets via hydrogen bonds, hydrophobic bonds and van der Waals forces. Based on the emerging PROTAC technology and the existing 3CL inhibitors, 3CL PROTAC degraders are hypothesised to be next-generation anti-coronavirus drugs.

摘要

本综述全面描述了 2010 年至 2020 年开发的冠状病毒 3CL 肽拟肽抑制剂和非肽小分子抑制剂。具体而言，通过分为两类详细阐述了这些 3CL 抑制剂的结构特征、结合模式和 SAR：肽拟肽抑制剂主要利用亲电弹头基团与 3CL Cys145 残基共价结合，从而实现不可逆的抑制效果，而非肽小分子抑制剂主要通过氢键、疏水键和范德华力与 S1'、S1、S2 和 S4 口袋中的残基相互作用。基于新兴的 PROTAC 技术和现有的 3CL 抑制剂，假设 3CL PROTAC 降解剂将成为下一代抗冠状病毒药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/98edaba2fe5d/gr20_lrg.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/c7608e3a8df8/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/ae668f04d198/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/aafdd64e0a80/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/9471f95a7cbb/gr5_lrg.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/55ec20929ee8/gr19_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/98edaba2fe5d/gr20_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/d151d323ecd6/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/66b86e304567/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/c7608e3a8df8/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/ae668f04d198/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/aafdd64e0a80/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/9471f95a7cbb/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/63eda495ad21/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/0274894e0dde/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/ba224c477ca3/gr8_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/e34bfc51ed48/gr9_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/6ce0096bdca8/gr10_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/06cecace5733/gr11_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/563ce6c07eed/gr12_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/6b9803a09a4e/gr13_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/8b42bdd5ef8b/gr14_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/41c99453ff62/gr15_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/e16772e6872d/gr16_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/90f1b61bcc29/gr17_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/17a17b97cda4/gr18_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/55ec20929ee8/gr19_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/7409838/98edaba2fe5d/gr20_lrg.jpg

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