A siRNA targets and inhibits a broad range of SARS‐CoV‐2 infections including Delta variant
Abstract The emergence of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) variants has altered the trajectory of the COVID‐19 pandemic and raised some uncertainty on the long‐term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS‐CoV‐2 vari...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2022-02-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202115298 |
| _version_ | 1827045156267753472 |
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| author | Yi‐Chung Chang Chi‐Fan Yang Yi‐Fen Chen Chia‐Chun Yang Yuan‐Lin Chou Hung‐Wen Chou Tein‐Yao Chang Tai‐Ling Chao Shu‐Chen Hsu Si‐Man Ieong Ya‐Min Tsai Ping‐Cheng Liu Yuan‐Fan Chin Jun‐Tung Fang Han‐Chieh Kao Hsuan‐Ying Lu Jia‐Yu Chang Ren‐Shiuan Weng Qian‐Wen Tu Fang‐Yu Chang Kuo‐Yen Huang Tong‐Young Lee Sui‐Yuan Chang Pan‐Chyr Yang |
| author_facet | Yi‐Chung Chang Chi‐Fan Yang Yi‐Fen Chen Chia‐Chun Yang Yuan‐Lin Chou Hung‐Wen Chou Tein‐Yao Chang Tai‐Ling Chao Shu‐Chen Hsu Si‐Man Ieong Ya‐Min Tsai Ping‐Cheng Liu Yuan‐Fan Chin Jun‐Tung Fang Han‐Chieh Kao Hsuan‐Ying Lu Jia‐Yu Chang Ren‐Shiuan Weng Qian‐Wen Tu Fang‐Yu Chang Kuo‐Yen Huang Tong‐Young Lee Sui‐Yuan Chang Pan‐Chyr Yang |
| author_sort | Yi‐Chung Chang |
| collection | DOAJ |
| description | Abstract The emergence of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) variants has altered the trajectory of the COVID‐19 pandemic and raised some uncertainty on the long‐term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS‐CoV‐2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS‐CoV‐2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma, and Epsilon, at picomolar ranges of IC50in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by cotreatment in K18‐hACE2‐transgenic mice, accompanied by a significant prevention of virus‐associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggest that C6G25S provides an alternative and effective approach to combating the COVID‐19 pandemic. |
| first_indexed | 2024-03-07T17:38:12Z |
| format | Article |
| id | doaj.art-b59c23cca78f41b498973507e9a76ace |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-18T14:20:01Z |
| publishDate | 2022-02-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-b59c23cca78f41b498973507e9a76ace2024-10-28T08:50:50ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842022-02-0114411810.15252/emmm.202115298A siRNA targets and inhibits a broad range of SARS‐CoV‐2 infections including Delta variantYi‐Chung Chang0Chi‐Fan Yang1Yi‐Fen Chen2Chia‐Chun Yang3Yuan‐Lin Chou4Hung‐Wen Chou5Tein‐Yao Chang6Tai‐Ling Chao7Shu‐Chen Hsu8Si‐Man Ieong9Ya‐Min Tsai10Ping‐Cheng Liu11Yuan‐Fan Chin12Jun‐Tung Fang13Han‐Chieh Kao14Hsuan‐Ying Lu15Jia‐Yu Chang16Ren‐Shiuan Weng17Qian‐Wen Tu18Fang‐Yu Chang19Kuo‐Yen Huang20Tong‐Young Lee21Sui‐Yuan Chang22Pan‐Chyr Yang23Oneness Biotech Company LimitedMicrobio (Shanghai) Biotech CompanyOneness Biotech Company LimitedMicrobio (Shanghai) Biotech CompanyMicrobio (Shanghai) Biotech CompanyOneness Biotech Company LimitedInstitute of Preventive Medicine, National Defense Medical CenterDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of MedicineInstitute of Preventive Medicine, National Defense Medical CenterDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of MedicineDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of MedicineInstitute of Preventive Medicine, National Defense Medical CenterInstitute of Preventive Medicine, National Defense Medical CenterDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of MedicineDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of MedicineInstitute of Preventive Medicine, National Defense Medical CenterInstitute of Preventive Medicine, National Defense Medical CenterOneness Biotech Company LimitedOneness Biotech Company LimitedOneness Biotech Company LimitedInstitute of Microbiology and Immunology, National Defense Medical CenterMicrobio (Shanghai) Biotech CompanyDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of MedicineDepartment of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of MedicineAbstract The emergence of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) variants has altered the trajectory of the COVID‐19 pandemic and raised some uncertainty on the long‐term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS‐CoV‐2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS‐CoV‐2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma, and Epsilon, at picomolar ranges of IC50in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by cotreatment in K18‐hACE2‐transgenic mice, accompanied by a significant prevention of virus‐associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggest that C6G25S provides an alternative and effective approach to combating the COVID‐19 pandemic.https://doi.org/10.15252/emmm.202115298COVID‐19inhalationK18‐hACE2‐transgenic miceSARS‐CoV‐2siRNA |
| spellingShingle | Yi‐Chung Chang Chi‐Fan Yang Yi‐Fen Chen Chia‐Chun Yang Yuan‐Lin Chou Hung‐Wen Chou Tein‐Yao Chang Tai‐Ling Chao Shu‐Chen Hsu Si‐Man Ieong Ya‐Min Tsai Ping‐Cheng Liu Yuan‐Fan Chin Jun‐Tung Fang Han‐Chieh Kao Hsuan‐Ying Lu Jia‐Yu Chang Ren‐Shiuan Weng Qian‐Wen Tu Fang‐Yu Chang Kuo‐Yen Huang Tong‐Young Lee Sui‐Yuan Chang Pan‐Chyr Yang A siRNA targets and inhibits a broad range of SARS‐CoV‐2 infections including Delta variant EMBO Molecular Medicine COVID‐19 inhalation K18‐hACE2‐transgenic mice SARS‐CoV‐2 siRNA |
| title | A siRNA targets and inhibits a broad range of SARS‐CoV‐2 infections including Delta variant |
| title_full | A siRNA targets and inhibits a broad range of SARS‐CoV‐2 infections including Delta variant |
| title_fullStr | A siRNA targets and inhibits a broad range of SARS‐CoV‐2 infections including Delta variant |
| title_full_unstemmed | A siRNA targets and inhibits a broad range of SARS‐CoV‐2 infections including Delta variant |
| title_short | A siRNA targets and inhibits a broad range of SARS‐CoV‐2 infections including Delta variant |
| title_sort | sirna targets and inhibits a broad range of sars cov 2 infections including delta variant |
| topic | COVID‐19 inhalation K18‐hACE2‐transgenic mice SARS‐CoV‐2 siRNA |
| url | https://doi.org/10.15252/emmm.202115298 |
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