| Autor: |
Yusen Xiang, Guanglei Zhai, Yaozong Li, Mengge Wang, Xixiang Chen, Ruyu Wang, Hang Xie, Weidong Zhang, Guangbo Ge, Qian Zhang, Yechun Xu, Amedeo Caflisch, Jianrong Xu, Hongzhuan Chen, Lili Chen |
| Přispěvatelé: |
University of Zurich, Xu, Jianrong |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
International journal of biological macromolecules. |
| ISSN: |
1879-0003 |
| Popis: |
Targeting the interaction between the spike protein receptor binding domain (S-RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2) is a potential therapeutic strategy for treating coronavirus disease 2019 (COVID-19). However, we still lack small-molecule drug candidates for this target due to the missing knowledge in the hot spots for the protein-protein interaction. Here, we used NanoBiT technology to identify three Ginkgolic acids from an in-house traditional Chinese medicine (TCM) library, and they interfere with the S-RBD/ACE2 interplay. Our pseudovirus assay showed that one of the compounds, Ginkgolic acid C17:1 (GA171), significantly inhibits the entry of original SARS-CoV-2 and its variants into the ACE2-overexpressed HEK293T cells. We investigated and proposed the binding sites of GA171 on S-RBD by combining molecular docking and molecular dynamics simulations. Site-directed mutagenesis and surface plasmon resonance revealed that GA171 specifically binds to the pocket near R403 and Y505, critical residues of S-RBD for S-RBD interacting with ACE2. Thus, we provide structural insights into developing new small-molecule inhibitors and vaccines against the proposed S-RBD binding site. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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