Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris

被引：244

作者：

Thi Thanh Hanh Nguyen ^{[1
,2
,3
]}

Woo, Hye-Jin ^{[1
,2
,3
]}

Kang, Hee-Kyoung ^{[1
,2
,3
]}

Van Dao Nguyen ^{[4
]}

Kim, Young-Min ^{[5
]}

Kim, Do-Won ^{[6
]}

Ahn, Sul-Ah ^{[7
]}

Xia, Yongmei ^{[8
]}

Kim, Doman ^{[1
,2
,3
]}

机构：

[1] Chonnam Natl Univ, Sch Biol Sci & Technol, Kwangju 500757, South Korea

[2] Chonnam Natl Univ, Res Inst Catalysis, Kwangju 500757, South Korea

[3] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA

[4] Hanoi Open Univ, Biotechnol Fac, Hanoi, Vietnam

[5] Korea Res Inst Biosci & Biotechnol, Ecofriendly Biomat Res Ctr, Jeongeup 580185, South Korea

[6] Gangeung Wonju Natl Univ, Dept Phys, Kangnung 210702, South Korea

[7] Korea Inst Sci & Technol Informat, Global Sci Expt Data Hub Ctr, Taejon 805306, South Korea

[8] Jiangnan Univ, State Key Lab Food Sci & Technol, Wuxi 214122, Jiangsu, Peoples R China

来源：

BIOTECHNOLOGY LETTERS | 2012年 / 34卷 / 05期

关键词：

Flavonoid; Molecular docking; Pichia pastoris; Protease; Severe acute respiratory syndrome (SARS);

D O I：

10.1007/s10529-011-0845-8

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Recombinant 3CL(pro) was expressed in GS115 as a 42 kDa protein that displayed a of 15 +/- A 2 mu M with Dabcyl-KTSAVLQSGFRKME-Edans as substrate. Purified 3CL(pro) was used for inhibition and kinetic assays with seven flavonoid compounds. The IC50 of six flavonoid compounds were 47-381 mu M. Quercetin, epigallocatechin gallate and gallocatechin gallate (GCG) displayed good inhibition toward 3CL(pro) with IC50 values of 73, 73 and 47 mu M, respectively. GCG showed a competitive inhibition pattern with value of 25 +/- A 1.7 mu M. In molecular docking experiments, GCG displayed a binding energy of -14 kcal mol(-1) to the active site of 3CL(pro) and the galloyl moiety at 3-OH position was required for 3CL(pro) inhibition activity.

引用

页码：831 / 838

页数：8

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