Structure-Based Discovery and Structural Basis of a Novel Broad-Spectrum Natural Product against the Main Protease of Coronavirus
Yuting Zhang, Hongxia Gao, Xiaohui Hu, Qisheng Wang, Fanglin Zhong, Xuelan Zhou, Cheng Lin, Yang Yang, Junkang Wei, Weian Du, Huaiqiu Huang, Huan Zhou, Wei He, Hua Zhang, Yuting Zhang, Peter James McCormick, Jinheng Fu, Dan Wang, Yang Fu, Xiaolu Lu · Journal of Virology · 2021
The current pandemic has created an urgent need for broad-spectrum inhibitors of SARS-CoV-2. The main protease is relatively conservative compared to the spike protein and, thus, is one of the most promising targets in developing anti-coronavirus agents. We solved the crystal structures of the main protease of SARS-CoV and HCoV-NL63 that bound to shikonin. The structures provide important insights, have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational design of broad-spectrum anti-coronavirus ligands as new therapeutic agents.