Teicoplanin derivatives block spike protein mediated viral entry as pan-SARS-CoV-2 inhibitors
The rapid emergence of highly transmissible SARS-CoV-2 variants poses serious threat to the efficacy of vaccines and neutralizing antibodies. Thus, there is an urgent need to develop new and effective inhibitors against SARS-CoV-2 and future outbreaks. Here, we have identified a series of glycopepti...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S075333222300001X |
| _version_ | 1811177304562335744 |
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| author | Ling Ma Yali Li Ting Shi Zhiling Zhu Jianyuan zhao Yongli Xie Jiajia Wen Saisai Guo Jing Wang Jiwei Ding Chen Liang Guangzhi Shan Quanjie Li Mei Ge Shan Cen |
| author_facet | Ling Ma Yali Li Ting Shi Zhiling Zhu Jianyuan zhao Yongli Xie Jiajia Wen Saisai Guo Jing Wang Jiwei Ding Chen Liang Guangzhi Shan Quanjie Li Mei Ge Shan Cen |
| author_sort | Ling Ma |
| collection | DOAJ |
| description | The rapid emergence of highly transmissible SARS-CoV-2 variants poses serious threat to the efficacy of vaccines and neutralizing antibodies. Thus, there is an urgent need to develop new and effective inhibitors against SARS-CoV-2 and future outbreaks. Here, we have identified a series of glycopeptide antibiotics teicoplanin derivatives that bind to the SARS-CoV-2 spike (S) protein, interrupt its interaction with ACE2 receptor and selectively inhibit viral entry mediated by S protein. Computation modeling predicts that these compounds interact with the residues in the receptor binding domain. More importantly, these teicoplanin derivatives inhibit the entry of both pseudotyped SARS-CoV-2 Delta and Omicron variants. Our study demonstrates the feasibility of developing small molecule entry inhibitors by targeting the interaction of viral S protein and ACE2. Together, considering the proven safety and pharmacokinetics of teicoplanin as a glycopeptide antibiotic, the teicoplanin derivatives hold great promise of being repurposed as pan-SARS-CoV-2 inhibitors. |
| first_indexed | 2024-04-10T22:59:34Z |
| format | Article |
| id | doaj.art-cf6d0a1faf3f4c1a97ea9fd2173354f2 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-10T22:59:34Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-cf6d0a1faf3f4c1a97ea9fd2173354f22023-01-14T04:26:12ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-02-01158114213Teicoplanin derivatives block spike protein mediated viral entry as pan-SARS-CoV-2 inhibitorsLing Ma0Yali Li1Ting Shi2Zhiling Zhu3Jianyuan zhao4Yongli Xie5Jiajia Wen6Saisai Guo7Jing Wang8Jiwei Ding9Chen Liang10Guangzhi Shan11Quanjie Li12Mei Ge13Shan Cen14Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, ChinaShanghai Laiyi Center for Biopharmaceutical R&D, Shanghai, ChinaState Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, ChinaLady Davis Institute for Medical Research and McGill AIDS Centre, Jewish General Hospital, Montreal, Quebec, CanadaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China; Corresponding authors.Shanghai Laiyi Center for Biopharmaceutical R&D, Shanghai, China; Corresponding authors.Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China; CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China; Corresponding author at: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China.The rapid emergence of highly transmissible SARS-CoV-2 variants poses serious threat to the efficacy of vaccines and neutralizing antibodies. Thus, there is an urgent need to develop new and effective inhibitors against SARS-CoV-2 and future outbreaks. Here, we have identified a series of glycopeptide antibiotics teicoplanin derivatives that bind to the SARS-CoV-2 spike (S) protein, interrupt its interaction with ACE2 receptor and selectively inhibit viral entry mediated by S protein. Computation modeling predicts that these compounds interact with the residues in the receptor binding domain. More importantly, these teicoplanin derivatives inhibit the entry of both pseudotyped SARS-CoV-2 Delta and Omicron variants. Our study demonstrates the feasibility of developing small molecule entry inhibitors by targeting the interaction of viral S protein and ACE2. Together, considering the proven safety and pharmacokinetics of teicoplanin as a glycopeptide antibiotic, the teicoplanin derivatives hold great promise of being repurposed as pan-SARS-CoV-2 inhibitors.http://www.sciencedirect.com/science/article/pii/S075333222300001XSARS-CoV-2Spike proteinAngiotensin converting enzyme 2TeicoplaninEntry inhibitor |
| spellingShingle | Ling Ma Yali Li Ting Shi Zhiling Zhu Jianyuan zhao Yongli Xie Jiajia Wen Saisai Guo Jing Wang Jiwei Ding Chen Liang Guangzhi Shan Quanjie Li Mei Ge Shan Cen Teicoplanin derivatives block spike protein mediated viral entry as pan-SARS-CoV-2 inhibitors Biomedicine & Pharmacotherapy SARS-CoV-2 Spike protein Angiotensin converting enzyme 2 Teicoplanin Entry inhibitor |
| title | Teicoplanin derivatives block spike protein mediated viral entry as pan-SARS-CoV-2 inhibitors |
| title_full | Teicoplanin derivatives block spike protein mediated viral entry as pan-SARS-CoV-2 inhibitors |
| title_fullStr | Teicoplanin derivatives block spike protein mediated viral entry as pan-SARS-CoV-2 inhibitors |
| title_full_unstemmed | Teicoplanin derivatives block spike protein mediated viral entry as pan-SARS-CoV-2 inhibitors |
| title_short | Teicoplanin derivatives block spike protein mediated viral entry as pan-SARS-CoV-2 inhibitors |
| title_sort | teicoplanin derivatives block spike protein mediated viral entry as pan sars cov 2 inhibitors |
| topic | SARS-CoV-2 Spike protein Angiotensin converting enzyme 2 Teicoplanin Entry inhibitor |
| url | http://www.sciencedirect.com/science/article/pii/S075333222300001X |
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