Ginkgolic acids inhibit SARS-CoV-2 and its variants by blocking the spike protein/ACE2 interplay
文献类型：期刊论文
| 作者 | Xiang, Yusen1; Zhai, Guanglei2; Li, Yaozong3,4; Wang, Mengge1; Chen, Xixiang1,5; Wang, Ruyu1; Xie, Hang6; Zhang, Weidong1,7; Ge, Guangbo1; Zhang, Qian8 |
| 刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
 |
| 出版日期 | 2023-01-31 |
| 卷号 | 226页码:780-792 |
| 关键词 | SARS-CoV-2 S-RBD Ginkgolic acid |
| ISSN号 | 0141-8130 |
| DOI | 10.1016/j.ijbiomac.2022.12.057 |
| 通讯作者 | Xu, Jianrong(janker.xu@gmail.com) ; Chen, Hongzhuan(yaoli@shsmu.edu.cn) ; Chen, Lili(llchen@shutcm.edu.cn) |
| 英文摘要 | 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 candi-dates 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 var-iants 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 sur-face 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. |
| WOS关键词 | RECEPTOR-BINDING DOMAIN ; MOLECULAR-DYNAMICS ; FORCE-FIELD ; CONSTRAINTS ; SIMULATION ; DOCKING ; CHARMM ; CELLS |
| 资助项目 | National Natural Science Foundation of China[82141203] ; Shanghai Municipal Science and Technology Major Project, China[ZD2021CY001] ; Shanghai Municipal Health Commission, China[ZY(2021-2023)-0103] ; Swedish Research Council, Sweden[VR 2019-00608] ; Excellence grant of the Swiss National Science Foundation, Switzerland[310030B_189363] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry ; Polymer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000906556300001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/304064]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Xu, Jianrong; Chen, Hongzhuan; Chen, Lili |
| 作者单位 | 1.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai Frontiers Sci Ctr TCM Chem Biol, Shanghai 201203, Peoples R China 2.Shanghai HighsLab Therapeut Inc, Shanghai 201203, Peoples R China 3.Univ Zurich, Dept Biochem, Winterthurer Str 190, CH-8057 Zurich, Switzerland 4.Umea Univ, Dept Chem, S-90187 Umea, Sweden 5.Shanghai Univ Tradit Chinese Med, Acad Integrat Med, 1200 Cailun Rd, Shanghai 201203, Peoples R China 6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 7.Shanghai Univ Tradit Chinese Med, Shanghai Inst Infect Dis & Biosafety, Inst Interdisciplinary Integrat Med Res, Shanghai 201203, Peoples R China 8.Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China 9.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, Shanghai 201203, Peoples R China 10.Shanghai Jiao Tong Univ, Shanghai Univ, Collaborat Innovat Ctr Translat Med, Sch Med, 280 South Chongqing Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xiang, Yusen,Zhai, Guanglei,Li, Yaozong,et al. Ginkgolic acids inhibit SARS-CoV-2 and its variants by blocking the spike protein/ACE2 interplay[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,2023,226:780-792. |
| APA | Xiang, Yusen.,Zhai, Guanglei.,Li, Yaozong.,Wang, Mengge.,Chen, Xixiang.,...&Chen, Lili.(2023).Ginkgolic acids inhibit SARS-CoV-2 and its variants by blocking the spike protein/ACE2 interplay.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,226,780-792. |
| MLA | Xiang, Yusen,et al."Ginkgolic acids inhibit SARS-CoV-2 and its variants by blocking the spike protein/ACE2 interplay".INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 226(2023):780-792. |
入库方式： OAI收割
来源：上海药物研究所
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