๐ Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris
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 Pichia pastoris GS115 as a 42 kDa protein that displayed a K m of 15 ยฑ 2 ฮผM with Dabcyl-KTSAVLQSGFRKME-Edans as substrate. Purified 3CL pro was used for inhibition and kinetic assays with seven flavonoid compounds. The IC 50 of six flavonoid compounds were 47-381 ฮผM. Quercetin, epigallocatechin gallate and gallocatechin gallate (GCG) displayed good inhibition toward 3CL pro with IC 50 values of 73, 73 and 47 ฮผM, respectively. GCG showed a competitive inhibition pattern with K i value of 25 ยฑ 1. 7 ฮผM. 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. ยฉ 2012 Springer Science+Business Media B. V.
author
๐ค Nguyen, Thi Thanh Hanh
๐ค Woo, Hye Jin
๐ค Kang, Hee Kyoung
๐ค Nguyen, Van Dao
๐ค Kim, Young Min
๐ค Kim, Do Won
๐ค Ahn, Sul Ah
๐ค Xia, Yongmei
๐ค Kim, Doman
year
โฐ 2012
journal
๐ Biotechnology Letters
issn
๐ 01415492 15736776
volume
34
number
5
page
831-838
citedbycount
15
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