Insights into Structures and Dynamics of Flavivirus Proteases from NMR Studies

International Journal of Molecular Sciences

CongBao Kang¹  Qingxin Li² 

[1] Experimental Drug Development Centre (EDDC), Agency for Science, Technology and Research (A*STAR), 10 Biopolis Road, Chromos, 05-01, Singapore 138670, Singapore;Guangdong Provincial Bioengineering Institute (Guangzhou Sugarcane Industry Research Institute), Guangdong Key Lab of Sugarcane Improvement & Biorefinery, Guangzhou 510316, China;

关键词: flavivirus;    Dengue virus;    Zika virus;    West Nile virus;    protease;    NMR;   

DOI  :  10.3390/ijms21072527

来源: DOAJ

【 摘 要 】

Nuclear magnetic resonance (NMR) spectroscopy plays important roles in structural biology and drug discovery, as it is a powerful tool to understand protein structures, dynamics, and ligand binding under physiological conditions. The protease of flaviviruses is an attractive target for developing antivirals because it is essential for the maturation of viral proteins. High-resolution structures of the proteases in the absence and presence of ligands/inhibitors were determined using X-ray crystallography, providing structural information for rational drug design. Structural studies suggest that proteases from Dengue virus (DENV), West Nile virus (WNV), and Zika virus (ZIKV) exist in open and closed conformations. Solution NMR studies showed that the closed conformation is predominant in solution and should be utilized in structure-based drug design. Here, we reviewed solution NMR studies of the proteases from these viruses. The accumulated studies demonstrated that NMR spectroscopy provides additional information to understand conformational changes of these proteases in the absence and presence of substrates/inhibitors. In addition, NMR spectroscopy can be used for identifying fragment hits that can be further developed into potent protease inhibitors.

【 授权许可】

Unknown