Xiaoxin Chen, Xiaodong Huang, Qinhai Ma, Petr Kuzmič, Biao Zhou, Sai Zhang, Jizheng Chen, Jinxin Xu, Bin Liu, Haiming Jiang, Wenjie Zhang, Chunguang Yang, Shiguan Wu, Jianzhou Huang, Haijun Li, Chaofeng Long, Xin Zhao, Hongrui Xu, Yanan Sheng, Yaoting Guo, Chuanying Niu, Lu Xue, Yong Xu, Jinsong Liu, Tianyu Zhang, James Spencer, Zhenzhen Zhu, Wenbin Deng, Xinwen Chen, Shu-Hui Chen, Nanshan Zhong, Xiaoli Xiong, Zifeng Yang
Although vaccines are available for SARS-CoV-2, antiviral drugs such as nirmatrelvir are still needed, particularly for individuals in whom vaccines are less effective, such as the immunocompromised, to prevent severe COVID-19. Here we report an α-ketoamide-based peptidomimetic inhibitor of the SARS-CoV-2 main protease (Mpro ), designated RAY1216. Enzyme inhibition kinetic analysis shows that RAY1216 has an inhibition constant of 8.4 nM and suggests that it dissociates about 12 times slower from Mpro compared with nirmatrelvir...
March 29, 2024: Nature Microbiology