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) expressed in Escherichia coli BL21 (DE3) and their structure activity relationship.

Results: ZIKV NS2B-NS3 was expressed in E. coli BL21(DE3) as a 35 kDa protein. It had a K of 26 µM with the fluorogenic peptide Dabcyl-KTSAVLQSGFRKME-Edan. The purified ZIKV NS2B-NS3 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 by 6.2-88%. Seven polyphenol compounds had IC ranging from 22 ± 0.2 to 112 ± 5.5 µM. Myricetin showed a mixed type inhibitory pattern against ZIKV NS2B-NS3 protease. Its IC value was 22 ± 0.2 µM with a K value of 8.9 ± 1.9 µM.

Conclusion: The chemical structure of a polyphenol compound and its inhibitory activity against ZIKV NS2B-NS3 can be explored to develop highly selective inhibitors against ZIKV NS2B-NS3.