Glycopeptide Antibiotic Teicoplanin Inhibits Cell Entry of SARS-CoV-2 by Suppressing the Proteolytic Activity of Cathepsin L
Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), public health worldwide has been greatly threatened. The development of an effective treatment for this infection is crucial and urgent but is hampered by the incompl...
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| Format: | Article |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.884034/full |
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| author | Fei Yu Ting Pan Ting Pan Feng Huang Feng Huang Ruosu Ying Jun Liu Jun Liu Huimin Fan Junsong Zhang Weiwei Liu Yingtong Lin Yaochang Yuan Tao Yang Rong Li Xu Zhang Xi Lv Qianyu Chen Anqi Liang Fan Zou Fan Zou Bingfeng Liu Fengyu Hu Xiaoping Tang Linghua Li Kai Deng Xin He Hui Zhang Hui Zhang Yiwen Zhang Xiancai Ma Xiancai Ma Xiancai Ma |
| author_facet | Fei Yu Ting Pan Ting Pan Feng Huang Feng Huang Ruosu Ying Jun Liu Jun Liu Huimin Fan Junsong Zhang Weiwei Liu Yingtong Lin Yaochang Yuan Tao Yang Rong Li Xu Zhang Xi Lv Qianyu Chen Anqi Liang Fan Zou Fan Zou Bingfeng Liu Fengyu Hu Xiaoping Tang Linghua Li Kai Deng Xin He Hui Zhang Hui Zhang Yiwen Zhang Xiancai Ma Xiancai Ma Xiancai Ma |
| author_sort | Fei Yu |
| collection | DOAJ |
| description | Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), public health worldwide has been greatly threatened. The development of an effective treatment for this infection is crucial and urgent but is hampered by the incomplete understanding of the viral infection mechanisms and the lack of specific antiviral agents. We previously reported that teicoplanin, a glycopeptide antibiotic that has been commonly used in the clinic to treat bacterial infection, significantly restrained the cell entry of Ebola virus, SARS-CoV, and MERS-CoV by specifically inhibiting the activity of cathepsin L (CTSL). Here, we found that the cleavage sites of CTSL on the spike proteins of SARS-CoV-2 were highly conserved among all the variants. The treatment with teicoplanin suppressed the proteolytic activity of CTSL on spike and prevented the cellular infection of different pseudotyped SARS-CoV-2 viruses. Teicoplanin potently prevented the entry of SARS-CoV-2 into the cellular cytoplasm with an IC50 of 2.038 μM for the Wuhan-Hu-1 reference strain and an IC50 of 2.116 μM for the SARS-CoV-2 (D614G) variant. The pre-treatment of teicoplanin also prevented SARS-CoV-2 infection in hACE2 mice. In summary, our data reveal that CTSL is required for both SARS-CoV-2 and SARS-CoV infection and demonstrate the therapeutic potential of teicoplanin for universal anti-CoVs intervention. |
| first_indexed | 2024-04-13T03:44:50Z |
| format | Article |
| id | doaj.art-9f6d477cfb394e8e9d3488b192945897 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-13T03:44:50Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-9f6d477cfb394e8e9d3488b1929458972022-12-22T03:04:03ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-04-011310.3389/fmicb.2022.884034884034Glycopeptide Antibiotic Teicoplanin Inhibits Cell Entry of SARS-CoV-2 by Suppressing the Proteolytic Activity of Cathepsin LFei Yu0Ting Pan1Ting Pan2Feng Huang3Feng Huang4Ruosu Ying5Jun Liu6Jun Liu7Huimin Fan8Junsong Zhang9Weiwei Liu10Yingtong Lin11Yaochang Yuan12Tao Yang13Rong Li14Xu Zhang15Xi Lv16Qianyu Chen17Anqi Liang18Fan Zou19Fan Zou20Bingfeng Liu21Fengyu Hu22Xiaoping Tang23Linghua Li24Kai Deng25Xin He26Hui Zhang27Hui Zhang28Yiwen Zhang29Xiancai Ma30Xiancai Ma31Xiancai Ma32Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Science, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaCenter for Infection and Immunity Study, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaBioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, ChinaGuangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaCenter for Infection and Immunity Study, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, ChinaGuangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangdong Provincial People’s Hospital, Guangdong Academy of Medical Science, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial People’s Hospital, Guangdong Academy of Medical Science, Guangzhou, ChinaGuangdong Provincial People’s Hospital, Guangdong Academy of Medical Science, Guangzhou, ChinaGuangdong Provincial People’s Hospital, Guangdong Academy of Medical Science, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaGuangzhou Women and Children Medical Center, Guangzhou Institute of Pediatrics, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaGuangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaNational Guangzhou Laboratory, Bio-Island, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial People’s Hospital, Guangdong Academy of Medical Science, Guangzhou, ChinaKey Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-sen University, Guangzhou, ChinaNational Guangzhou Laboratory, Bio-Island, Guangzhou, ChinaSince the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), public health worldwide has been greatly threatened. The development of an effective treatment for this infection is crucial and urgent but is hampered by the incomplete understanding of the viral infection mechanisms and the lack of specific antiviral agents. We previously reported that teicoplanin, a glycopeptide antibiotic that has been commonly used in the clinic to treat bacterial infection, significantly restrained the cell entry of Ebola virus, SARS-CoV, and MERS-CoV by specifically inhibiting the activity of cathepsin L (CTSL). Here, we found that the cleavage sites of CTSL on the spike proteins of SARS-CoV-2 were highly conserved among all the variants. The treatment with teicoplanin suppressed the proteolytic activity of CTSL on spike and prevented the cellular infection of different pseudotyped SARS-CoV-2 viruses. Teicoplanin potently prevented the entry of SARS-CoV-2 into the cellular cytoplasm with an IC50 of 2.038 μM for the Wuhan-Hu-1 reference strain and an IC50 of 2.116 μM for the SARS-CoV-2 (D614G) variant. The pre-treatment of teicoplanin also prevented SARS-CoV-2 infection in hACE2 mice. In summary, our data reveal that CTSL is required for both SARS-CoV-2 and SARS-CoV infection and demonstrate the therapeutic potential of teicoplanin for universal anti-CoVs intervention.https://www.frontiersin.org/articles/10.3389/fmicb.2022.884034/fullteicoplaninSARS-CoV-2spikecathepsin Lviral entry |
| spellingShingle | Fei Yu Ting Pan Ting Pan Feng Huang Feng Huang Ruosu Ying Jun Liu Jun Liu Huimin Fan Junsong Zhang Weiwei Liu Yingtong Lin Yaochang Yuan Tao Yang Rong Li Xu Zhang Xi Lv Qianyu Chen Anqi Liang Fan Zou Fan Zou Bingfeng Liu Fengyu Hu Xiaoping Tang Linghua Li Kai Deng Xin He Hui Zhang Hui Zhang Yiwen Zhang Xiancai Ma Xiancai Ma Xiancai Ma Glycopeptide Antibiotic Teicoplanin Inhibits Cell Entry of SARS-CoV-2 by Suppressing the Proteolytic Activity of Cathepsin L Frontiers in Microbiology teicoplanin SARS-CoV-2 spike cathepsin L viral entry |
| title | Glycopeptide Antibiotic Teicoplanin Inhibits Cell Entry of SARS-CoV-2 by Suppressing the Proteolytic Activity of Cathepsin L |
| title_full | Glycopeptide Antibiotic Teicoplanin Inhibits Cell Entry of SARS-CoV-2 by Suppressing the Proteolytic Activity of Cathepsin L |
| title_fullStr | Glycopeptide Antibiotic Teicoplanin Inhibits Cell Entry of SARS-CoV-2 by Suppressing the Proteolytic Activity of Cathepsin L |
| title_full_unstemmed | Glycopeptide Antibiotic Teicoplanin Inhibits Cell Entry of SARS-CoV-2 by Suppressing the Proteolytic Activity of Cathepsin L |
| title_short | Glycopeptide Antibiotic Teicoplanin Inhibits Cell Entry of SARS-CoV-2 by Suppressing the Proteolytic Activity of Cathepsin L |
| title_sort | glycopeptide antibiotic teicoplanin inhibits cell entry of sars cov 2 by suppressing the proteolytic activity of cathepsin l |
| topic | teicoplanin SARS-CoV-2 spike cathepsin L viral entry |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.884034/full |
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