Ginkgolic acids inhibit SARS-CoV-2 and its variants by blocking the spike protein/ACE2 interplay
Title | Ginkgolic acids inhibit SARS-CoV-2 and its variants by blocking the spike protein/ACE2 interplay |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Xiang Y., Zhai G., Li Y., Wang M., Chen X., Wang R., Xie H., Zhang W., Ge G., Zhang Q., Xu Y., Caflisch A., Xu J., Chen H., Chen L. |
Journal | International Journal of Biological Macromolecules |
Volume | 226 |
Pagination | 780-792 |
Date Published | 2023 Jan 31 |
Type of Article | Research Article |
ISSN | 1879-0003 |
Keywords | Angiotensin-Converting Enzyme 2, COVID-19, HEK293 Cells, Humans, Molecular Docking Simulation, Molecular Dynamics Simulation, Protein Binding, SARS-CoV-2, Spike Glycoprotein, Coronavirus |
Abstract | 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. |
DOI | 10.1016/j.ijbiomac.2022.12.057 |
pubindex | 0286 |
Alternate Journal | Int. J. Biol. Macromol. |
PubMed ID | 36521705 |
PubMed Central ID | PMC9743696 |