title: Inhibitory effect of flavonoids against NS2B-NS3 protease of ZIKA virus and their structure activity relationship.
abstract: OBJECTIVE
  To determine the inhibitory activities of flavonoids against NS2B-NS3 protease of ZIKA virus (ZIKV NS2B-NS3pro) expressed in Escherichia coli BL21 (DE3) and their structure activity relationship.
  
  
  RESULTS
  ZIKV NS2B-NS3prowas expressed in E. coli BL21(DE3) as a 35 kDa protein. It had a Kmof 26 µM with the fluorogenic peptide Dabcyl-KTSAVLQSGFRKME-Edan. The purified ZIKV NS2B-NS3prowas used for inhibition and kinetic assays to determine the activities of 22 polyphenol compounds. These polyphenol compounds at 100 µM inhibited the activity of ZIKV NS2B-NS3proby 6.2-88%. Seven polyphenol compounds had IC50ranging from 22 ± 0.2 to 112 ± 5.5 µM. Myricetin showed a mixed type inhibitory pattern against ZIKV NS2B-NS3proprotease. Its IC50value was 22 ± 0.2 µM with a Kivalue of 8.9 ± 1.9 µM.
  
  
  CONCLUSIONS
  The chemical structure of a polyphenol compound and its inhibitory activity against ZIKV NS2B-NS3procan be explored to develop highly selective inhibitors against ZIKV NS2B-NS3pro.
authors.affiliation: Graduate School of International Agricultural Technology and Institute of Food Industrialization, Institutes of Green Bioscience & Technology, Seoul National University, Pyeongchang-gun, Gangwon-do, 25354, South Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Lim
authors.affiliation: Graduate School of International Agricultural Technology and Institute of Food Industrialization, Institutes of Green Bioscience & Technology, Seoul National University, Pyeongchang-gun, Gangwon-do, 25354, South Korea.
authors.forename: Thi Thanh Hanh
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA, 90089, USA.
authors.forename: Nahyun M
authors.initials: NM
authors.lastname: Kim
authors.affiliation: Skin Research Institute, Amorepacific Corporation R&D Center, Yongin, 17074, South Korea.
authors.forename: Jun-Seong
authors.initials: JS
authors.lastname: Park
authors.affiliation: Graduate School of International Agricultural Technology and Institute of Food Industrialization, Institutes of Green Bioscience & Technology, Seoul National University, Pyeongchang-gun, Gangwon-do, 25354, South Korea.
authors.forename: Tae-Su
authors.initials: TS
authors.lastname: Jang
authors.affiliation: Graduate School of International Agricultural Technology and Institute of Food Industrialization, Institutes of Green Bioscience & Technology, Seoul National University, Pyeongchang-gun, Gangwon-do, 25354, South Korea. kimdm@snu.ac.kr.
authors.forename: Doman
authors.initials: D
authors.lastname: Kim
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071244:Zika Virus / Q000201:enzymology*
chemical_list: D005419:Flavonoids; D059808:Polyphenols; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins
keywords: Flavanoids; Myricetin; Polyphenols; Protease; Zika virus