Crystal structure of unlinked NS2B-NS3 protease from Zika virus

• Main Authors: Zhang, Zhenzhen, Li, Yan, Loh, Ying Ru, Phoo, Wint Wint, Hung, Alvin W., Kang, CongBao, Luo, Dahai
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2017
• Subjects: Crystal Structure; Zika Virus
• Online Access: https://hdl.handle.net/10356/84352; http://hdl.handle.net/10220/43576
• Institution: Nanyang Technological University

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 at 1.58-angstrom resolution of the unlinked NS2B-NS3 protease from ZIKV as free enzyme and bound to a peptide reversely oriented at the active site. 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 the discovery of structure-based antiviral drugs against ZIKV and related pathogenic flaviviruses.