Science 23 Dec 2016: Vol. 354, Issue 6319, pp. 1597-1600
Zika virus (ZIKV) has rapidly emerged as a global public health concern. Viral NS2B-NS3 protease processes viral polyprotein and is essential for the virus replication, making it an attractive antiviral drug target. We report crystal structures of the unlinked NS2B-NS3 protease from ZIKV as free enzyme and bound to a peptide reversely oriented at the active site at 1.58 Å resolution. The unlinked NS2B-NS3 protease adopts a closed conformation in which NS2B engages NS3 to form an empty substrate binding site. A second protease in the same crystal binds to the residues K14K15G16E17 from the neighboring NS3 in reverse orientation resisting proteolysis. These features of ZIKV NS2B-NS3 protease may accelerate structure-based antiviral drug discovery against ZIKV and related pathogenic flaviviruses.
Lee Kong Chian School of Medicine, Nanyang Technological University, National Medical Research Council grant CBRG15May045, A*STAR JCO grant (1431AFG102/1331A028)