Phenothiazines Inhibit SARS-CoV-2 Entry through Targeting Spike Protein
Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and continues to threaten humanity due to the persistent emergence of new variants. Therefore, developing more ef...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/8/1666 |
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| author | Taizhen Liang Shiqi Xiao Ziyao Wu Xi Lv Sen Liu Meilin Hu Guojie Li Peiwen Li Xiancai Ma |
| author_facet | Taizhen Liang Shiqi Xiao Ziyao Wu Xi Lv Sen Liu Meilin Hu Guojie Li Peiwen Li Xiancai Ma |
| author_sort | Taizhen Liang |
| collection | DOAJ |
| description | Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and continues to threaten humanity due to the persistent emergence of new variants. Therefore, developing more effective and broad-spectrum therapeutic and prophylactic drugs against infection by SARS-CoV-2 and its variants, as well as future emerging CoVs, is urgently needed. In this study, we screened several US FDA-approved drugs and identified phenothiazine derivatives with the ability to potently inhibit the infection of pseudotyped SARS-CoV-2 and distinct variants of concern (VOCs), including B.1.617.2 (Delta) and currently circulating Omicron sublineages XBB and BQ.1.1, as well as pseudotyped SARS-CoV and MERS-CoV. Mechanistic studies suggested that phenothiazines predominantly inhibited SARS-CoV-2 pseudovirus (PsV) infection at the early stage and potentially bound to the spike (S) protein of SARS-CoV-2, which may prevent the proteolytic cleavage of the S protein, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that phenothiazines can serve as a potential broad-spectrum therapeutic drug for the treatment of SARS-CoV-2 infection as well as the infection of future emerging human coronaviruses (HCoVs). |
| first_indexed | 2024-03-10T23:31:13Z |
| format | Article |
| id | doaj.art-f8d689662b78453481a5ac280552d730 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T23:31:13Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-f8d689662b78453481a5ac280552d7302023-11-19T03:19:58ZengMDPI AGViruses1999-49152023-07-01158166610.3390/v15081666Phenothiazines Inhibit SARS-CoV-2 Entry through Targeting Spike ProteinTaizhen Liang0Shiqi Xiao1Ziyao Wu2Xi Lv3Sen Liu4Meilin Hu5Guojie Li6Peiwen Li7Xiancai Ma8Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, ChinaGuangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, ChinaSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, ChinaSchool of Medicine, South China University of Technology, Guangzhou 510006, ChinaGuangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, ChinaGuangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, ChinaGuangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, ChinaGuangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, ChinaGuangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, ChinaNovel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and continues to threaten humanity due to the persistent emergence of new variants. Therefore, developing more effective and broad-spectrum therapeutic and prophylactic drugs against infection by SARS-CoV-2 and its variants, as well as future emerging CoVs, is urgently needed. In this study, we screened several US FDA-approved drugs and identified phenothiazine derivatives with the ability to potently inhibit the infection of pseudotyped SARS-CoV-2 and distinct variants of concern (VOCs), including B.1.617.2 (Delta) and currently circulating Omicron sublineages XBB and BQ.1.1, as well as pseudotyped SARS-CoV and MERS-CoV. Mechanistic studies suggested that phenothiazines predominantly inhibited SARS-CoV-2 pseudovirus (PsV) infection at the early stage and potentially bound to the spike (S) protein of SARS-CoV-2, which may prevent the proteolytic cleavage of the S protein, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that phenothiazines can serve as a potential broad-spectrum therapeutic drug for the treatment of SARS-CoV-2 infection as well as the infection of future emerging human coronaviruses (HCoVs).https://www.mdpi.com/1999-4915/15/8/1666SARS-CoV-2phenothiazineentry inhibitorspikecathepsin L |
| spellingShingle | Taizhen Liang Shiqi Xiao Ziyao Wu Xi Lv Sen Liu Meilin Hu Guojie Li Peiwen Li Xiancai Ma Phenothiazines Inhibit SARS-CoV-2 Entry through Targeting Spike Protein Viruses SARS-CoV-2 phenothiazine entry inhibitor spike cathepsin L |
| title | Phenothiazines Inhibit SARS-CoV-2 Entry through Targeting Spike Protein |
| title_full | Phenothiazines Inhibit SARS-CoV-2 Entry through Targeting Spike Protein |
| title_fullStr | Phenothiazines Inhibit SARS-CoV-2 Entry through Targeting Spike Protein |
| title_full_unstemmed | Phenothiazines Inhibit SARS-CoV-2 Entry through Targeting Spike Protein |
| title_short | Phenothiazines Inhibit SARS-CoV-2 Entry through Targeting Spike Protein |
| title_sort | phenothiazines inhibit sars cov 2 entry through targeting spike protein |
| topic | SARS-CoV-2 phenothiazine entry inhibitor spike cathepsin L |
| url | https://www.mdpi.com/1999-4915/15/8/1666 |
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