| Autor: |
Shi, Yulong, Chen, Fenbei, Wu, Mengyuan, Zhang, Xin, Meng, Runze, Wang, Kun, Wang, Yan, Mei, Yuheng, Duan, Qionglu, Li, Yinghong, Gao, Rongmei, Li, Yuhuan, Deng, Hongbin, Jiang, Jiandong, Wang, Yanxiang, Song, Danqing |
| Zdroj: |
Chinese Chemical Letters; 20230101, Issue: Preprints |
| Abstrakt: |
Thirty-one new 10,12-disubstituted aloperine derivatives were subtly constructed through a selective oxidation on the 10-α-C–H induced by sulfonyl and a nucleophilic substitution with the stereoselectivity and scalability. Of them, compound 6bdisplayed a moderate anti-human coronavirus OC43 (HCoV-OC43) potency and blocked the viral entry stage through a host mechanism of action. Using chemoproteomic techniques, both transmembrane serine protease 2 (TMPRSS2) and scavenger receptor class B type 1 (SR-B1) proteins, which act as host cofactors of viral entry, were identified to be the direct targets of 6bagainst HCoV-OC43. Furthermore, 6bmay deactivate the TMPRSS2 by inducing a change in protein conformation, rather than binding to its catalytic center, thus suppressing the viral membrane fusion. Accordingly, our study provided key scientific data for the development of aloperine derivatives into a new class of antiviral candidates against human β-coronavirus, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). |
| Databáze: |
Supplemental Index |
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