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

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 .