Inhibitory effect of flavonoids against NS2B-NS3 protease of ZIKA virus and their structure activity relationship

Lim, Hee-jung; Nguyen, Thi Thanh Hanh; Kim, Nahyun M.; Park, Jun-Seong; Jang, Tae-Su; Kim, Doman

OBJECTIVES: To determine the inhibitory activities of flavonoids against NS2B-NS3 protease of ZIKA virus (ZIKV NS2B-NS3(pro)) expressed in Escherichia coli BL21 (DE3) and their structure activity relationship. RESULTS: ZIKV NS2B-NS3(pro) was expressed in E. coli BL21(DE3) as a 35 kDa protein. It had a K (m) of 26 µM with the fluorogenic peptide Dabcyl-KTSAVLQSGFRKME-Edan. The purified ZIKV NS2B-NS3(pro) was 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-NS3(pro) by 6.2–88%. Seven polyphenol compounds had IC(50) ranging from 22 ± 0.2 to 112 ± 5.5 µM. Myricetin showed a mixed type inhibitory pattern against ZIKV NS2B-NS3(pro) protease. Its IC(50) value was 22 ± 0.2 µM with a K (i) value of 8.9 ± 1.9 µM. CONCLUSION: The chemical structure of a polyphenol compound and its inhibitory activity against ZIKV NS2B-NS3(pro) can be explored to develop highly selective inhibitors against ZIKV NS2B-NS3(pro). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10529-016-2261-6) contains supplementary material, which is available to authorized users.