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

被引：238

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

共 17 条

[1] Benson DA, 2013, NUCLEIC ACIDS RES, V41, pD36, DOI [10.1093/nar/gkn723, 10.1093/nar/gkp1024, 10.1093/nar/gkw1070, 10.1093/nar/gkr1202, 10.1093/nar/gkx1094, 10.1093/nar/gkl986, 10.1093/nar/gkq1079, 10.1093/nar/gks1195, 10.1093/nar/gkg057]
[2] Inhibition of SARS-CoV 3C-like protease activity by theaflavin-3,3′- digallate (TF3)
Chen, CN
Lin, CPC
Huang, KK
Chen, WC
Hsieh, HP
Liang, PH
Hsu, JTA
[J]. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE, 2005, 2 (02) : 209 - 215
[3] Binding interaction of quereetin-3-β-galactoside and its synthetic derivatives with SARS-CoV 3CLpro:: Structure-activity relationship studies reveal salient pharmacophore features
Chen, Lili
Li, Jian
Luo, Cheng
Liu, Hong
Xu, Weijun
Chen, Gang
Liew, Oi Wah
Zhu, Weiliang
Puah, Chum Mok
Shen, Xu
Jiang, Hualiang
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (24) : 8295 - 8306
[4] de Groot H, 1998, FUND CLIN PHARMACOL, V12, P249
[5] Evaluating the 3C-like protease activity of SARS-Coronavirus: Recommendations for standardized assays for drug discovery
Grum-Tokars, Valerie
Ratia, Kiira
Begaye, Adrian
Baker, Susan C.
Mesecar, Andrew D.
[J]. VIRUS RESEARCH, 2008, 133 (01) : 63 - 73
[6] Characterization of SARS main protease and inhibitor assay using a fluorogenic substrate
Kuo, CJ
Chi, YH
Hsu, JTA
Liang, PH
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 318 (04) : 862 - 867
[7] Structural Basis of Inhibition Specificities of 3C and 3C-like Proteases by Zinc-coordinating and Peptidomimetic Compounds
Lee, Cheng-Chung
Kuo, Chih-Jung
Ko, Tzu-Ping
Hsu, Min-Feng
Tsui, Yao-Chen
Chang, Shih-Cheng
Yang, Syaulan
Chen, Shu-Jen
Chen, Hua-Chien
Hsu, Ming-Chu
Shih, Shin-Ru
Liang, Po-Huang
Wang, Andrew H. -J.
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (12) : 7646 - 7655
[8] Morris GM, 1998, J COMPUT CHEM, V19, P1639, DOI 10.1002/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO
[9] 2-B
[10] Characterization of a novel coronavirus associated with severe acute respiratory syndrome
Rota, PA
Oberste, MS
Monroe, SS
Nix, WA
Campagnoli, R
Icenogle, JP
Peñaranda, S
Bankamp, B
Maher, K
Chen, MH
Tong, SX
Tamin, A
Lowe, L
Frace, M
DeRisi, JL
Chen, Q
Wang, D
Erdman, DD
Peret, TCT
Burns, C
Ksiazek, TG
Rollin, PE
Sanchez, A
Liffick, S
Holloway, B
Limor, J
McCaustland, K
Olsen-Rasmussen, M
Fouchier, R
Günther, S
Osterhaus, ADME
Drosten, C
Pallansch, MA
Anderson, LJ
Bellini, WJ
[J]. SCIENCE, 2003, 300 (5624) : 1394 - 1399

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