Structure-Based Virtual Screening and Identification of Potential Inhibitors of SARS-CoV-2 S-RBD and ACE2 Interaction
oleh: Jiacheng Xiong, Jiacheng Xiong, Yusen Xiang, Ziming Huang, Ziming Huang, Xiaohong Liu, Xiaohong Liu, Xiaohong Liu, Mengge Wang, Guangbo Ge, Hongzhuan Chen, Jianrong Xu, Jianrong Xu, Mingyue Zheng, Mingyue Zheng, Lili Chen
| Format: | Article |
|---|---|
| Diterbitkan: | Frontiers Media S.A. 2021-09-01 |
Deskripsi
The emergence and rapid spread of SARS-CoV-2 have caused a worldwide public health crisis. Designing small molecule inhibitors targeting SARS-CoV-2 S-RBD/ACE2 interaction is considered as a potential strategy for the prevention and treatment of SARS-CoV-2. But to date, only a few compounds have been reported as SARS-CoV-2 S-RBD/ACE2 interaction inhibitors. In this study, we described the virtual screening and experimental validation of two novel inhibitors (DC-RA016 and DC-RA052) against SARS-CoV-2 S-RBD/ACE2 interaction. The NanoBiT assays and surface plasmon resonance (SPR) assays demonstrated their capabilities of blocking SARS-CoV-2 S-RBD/ACE2 interaction and directly binding to both S-RBD and ACE2. Moreover, the pseudovirus assay revealed that these two compounds possessed significant antiviral activity (about 50% inhibition rate at maximum non-cytotoxic concentration). These results indicate that the compounds DC-RA016 and DC-RA052 are promising inhibitors against SARS-CoV-2 S-RBD/ACE2 interaction and deserve to be further developed.