Andrographolide and its fluorescent derivative inhibit the main proteases of 2019-nCoV and SARS-CoV through covalent linkage

被引：99

作者：

Shi, Tzu-Hau ^{[1
,2
,3
]}

Huang, Yi-Long ^{[4
]}

Chen, Chiao-Che ^{[1
,2
]}

Pi, Wen-Chieh ^{[5
]}

Hsu, Yu-Ling ^{[6
]}

Lo, Lee-Chiang ^{[6
]}

Chen, Wei-Yi ^{[5
]}

Fu, Shu-Ling ^{[7
]}

Lin, Chao-Hsiung ^{[1
,2
,4
,8
]}

机构：

[1] Natl Yang Ming Univ, Dept Life Sci, Taipei 112, Taiwan

[2] Natl Yang Ming Univ, Inst Genome Sci, Taipei 112, Taiwan

[3] Natl Yang Ming Univ, Biomed Ind PhD Program, Taipei 112, Taiwan

[4] Natl Yang Ming Univ, Aging & Hlth Res Ctr, Taipei 112, Taiwan

[5] Natl Yang Ming Univ, Inst Biochem & Mol Biol, Taipei 112, Taiwan

[6] Natl Taiwan Univ, Dept Chem, Taipei 106, Taiwan

[7] Natl Yang Ming Univ, Inst Tradit Med, Taipei 112, Taiwan

[8] Natl Yang Ming Univ, Inst Biopharmaceut Sci, Taipei 112, Taiwan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2020年 / 533卷 / 03期

关键词：

2019-nCoV; SARS-CoV; Main protease; Andrographolide; NATURAL-PRODUCTS; CORONAVIRUS;

D O I：

10.1016/j.bbrc.2020.08.086

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The coronavirus disease 2019 (COVID-19) pandemic caused by 2019 novel coronavirus (2019-nCoV) has been a crisis of global health, whereas the effective vaccines against 2019-nCoV are still under development. Alternatively, utilization of old drugs or available medicine that can suppress the viral activity or replication may provide an urgent solution to suppress the rapid spread of 2019-nCoV. Andrographolide is a highly abundant natural product of the medicinal plant, Andrographis paniculata, which has been clinically used for inflammatory diseases and anti-viral therapy. We herein demonstrate that both andrographolide and its fluorescent derivative, the nitrobenzoxadiazole-conjugated andrographolide (Andro-NBD), suppressed the main protease (M-pro) activities of 2019-nCoV and severe acute respiratory syndrome coronavirus (SARS-CoV). Moreover, Andro-NBD was shown to covalently link its fluorescence to these proteases. Further mass spectrometry (MS) analysis suggests that andrographolide formed a covalent bond with the active site Cys145 of either 2019-nCoV M-pro or SARS-CoV M-pro. Consistently, molecular modeling analysis supported the docking of andrographolide within the catalytic pockets of both viral M(pro)s. Considering that andrographolide is used in clinical practice with acceptable safety and its diverse pharmacological activities that could be beneficial for attenuating COVID-19 symptoms, extensive investigation of andrographolide on the suppression of 2019-nCoV as well as its application in COVID-19 therapy is suggested. (C) 2020 Elsevier Inc. All rights reserved.

引用

页码：467 / 473

页数：7

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