SARS-CoV-2 M <sup>pro</sup> inhibitors with antiviral activity in a transgenic mouse model
Jingxin Qiao, Yueshan Li, Rui Zeng, Feng‐Liang Liu, Rong‐Hua Luo, Chong Huang, Yifei Wang, Jie Zhang, Baoxue Quan, C. Shen, Xin Mao, Xinlei Liu, Weining Sun, Wei Yang, Xincheng Ni, Kai Wang, Ling Xu, Zilei Duan, Qing-Cui Zou, Hai-Lin Zhang, Wang Qu, Yanghaopeng Long, Minghua Li, Ruicheng Yang, Xiaolong Liu, Jing You, Yangli Zhou, Rui Yao, Wenpei Li, Jing-Ming Liu, Pei Chen, Yang Liu, Guifeng Lin, Xin Yang, Jun Zou, Linli Li, Yiguo Hu, Guangwen Lu, Weimin Li, Yuquan Wei, Yong‐Tang Zheng, Jian Lei, Shengyong Yang
Abstract
Targeting the SARS-CoV-2 main protease Vaccines are an important tool in the fight against COVID-19, but developing antiviral drugs is also a high priority, especially with the rise of variants that may partially evade vaccines. The viral protein main protease is required for cleaving precursor polyproteins into functional viral proteins. This essential function makes it a key drug target. Qiao et al. designed 32 inhibitors based on either boceprevir or telaprevir, both of which are protease inhibitors approved to treat hepatitis C virus. Six compounds protected cells from viral infection with high potency, and two of these were selected for in vivo studies based on pharmokinetic experiments. Both showed strong antiviral activity in a mouse model. Science , this issue p. 1374