Runze Meng, Xiuli Zhong, Yue Gong, Yulong Shi, Jiayu Li, Zhiyun Wu, Qionglu Duan, Xintong Zhang, Yuheng Mei, Jingyang Zhu, Zonggen Peng, Yinghong Li, Danqing Song
By inducing steric activation of the 10CH bond with a 12-acyl group to form a key imine oxime intermediate, 20 novel (10S)-10,12-disubstituted aloperine derivatives were successfully synthesized and assessed for their antiviral efficacy against HCoV-OC43. Of them, compound 3i exhibited the moderate activities against HCoV-OC43, as well as against the SARS-CoV-2 variant EG.5.1 with the comparable EC50 values of 4.7 and 4.1 μM. A mechanism study revealed that it inhibited the protease activity of host TMPRSS2 by binding to an allosteric site, rather than the known catalytic center, different from that of camostat...
March 27, 2024: Bioorganic Chemistry