Investigating non-nucleoside inhibitors targeting the Zika virus non-structural protein 5 (NS5) RNA-dependent RNA polymerase (RdRp) domain

• Main Author: Zhang, Denzel Xugeng
• Other Authors: Julien Lescar
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2022
• Subjects: Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/157309
• Institution: Nanyang Technological University

Zika virus and members of the Flaviviridae family are re-emerging pathogens that pose a significant threat to public health. The lack of a vaccine and specific treatment of has resulted in a need for the design of therapeutic treatments to target specific parts of virus replication cycles. Here, the RNA dependent RNA Polymerase (RdRP) of Zika Virus was purified based on previously established protocols. Fluorescence-based alkaline phosphatase coupled polymerase assay (FAPA), was used to screen a library of 86 compounds generated to target the Zika Virus NS5 RdRP. Hit compounds identified were tested for dose-response inhibition. Finally, crystallization efforts were carried out in hopes of obtaining crystal structures of inhibitor compounds in complex with the Zika NS5 RdRp protein.