Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients
Abstract Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-12-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-021-00835-6 |
| _version_ | 1818344214858039296 |
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| author | Jin-Lan Zhang Yu-Huan Li Lu-Lu Wang Hong-Qi Liu Shuai-Yao Lu Yong Liu Ke Li Bin Liu Su-Yun Li Feng-Min Shao Kun Wang Ning Sheng Rui Li Jin-Jin Cui Pei-Chun Sun Chun-Xia Ma Bo Zhu Zhe Wang Yuan-Hao Wan Shi-Shan Yu Yongsheng Che Chao-Yang Wang Chen Wang Qiangqian Zhang Li-Min Zhao Xiao-Zhong Peng Zhenshun Cheng Jun-Biao Chang Jian-Dong Jiang |
| author_facet | Jin-Lan Zhang Yu-Huan Li Lu-Lu Wang Hong-Qi Liu Shuai-Yao Lu Yong Liu Ke Li Bin Liu Su-Yun Li Feng-Min Shao Kun Wang Ning Sheng Rui Li Jin-Jin Cui Pei-Chun Sun Chun-Xia Ma Bo Zhu Zhe Wang Yuan-Hao Wan Shi-Shan Yu Yongsheng Che Chao-Yang Wang Chen Wang Qiangqian Zhang Li-Min Zhao Xiao-Zhong Peng Zhenshun Cheng Jun-Biao Chang Jian-Dong Jiang |
| author_sort | Jin-Lan Zhang |
| collection | DOAJ |
| description | Abstract Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 μM, depending on viruses or cells, and selective index (SI) in 15–83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1–9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2–25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity. |
| first_indexed | 2024-12-13T16:42:56Z |
| format | Article |
| id | doaj.art-2b9e28f6b8454fbc95a8d8fb4f08409e |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-12-13T16:42:56Z |
| publishDate | 2021-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-2b9e28f6b8454fbc95a8d8fb4f08409e2022-12-21T23:38:14ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352021-12-016111510.1038/s41392-021-00835-6Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patientsJin-Lan Zhang0Yu-Huan Li1Lu-Lu Wang2Hong-Qi Liu3Shuai-Yao Lu4Yong Liu5Ke Li6Bin Liu7Su-Yun Li8Feng-Min Shao9Kun Wang10Ning Sheng11Rui Li12Jin-Jin Cui13Pei-Chun Sun14Chun-Xia Ma15Bo Zhu16Zhe Wang17Yuan-Hao Wan18Shi-Shan Yu19Yongsheng Che20Chao-Yang Wang21Chen Wang22Qiangqian Zhang23Li-Min Zhao24Xiao-Zhong Peng25Zhenshun Cheng26Jun-Biao Chang27Jian-Dong Jiang28State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical CollegeInstitute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical CollegeState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical CollegeInstitute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical CollegeInstitute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical CollegeGenuine Biotech. Inc.Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical CollegeDepartment of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan Research Center for Infectious Diseases and CancerThe First Affiliated Hospital of Henan University of Chinese MedicineDepartment of Internal Medicine, Henan Provincial Peoples HospitalInstitute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical CollegeState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical CollegeState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical CollegeInstitute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical CollegeDepartment of Internal Medicine, Henan Provincial Peoples HospitalInstitute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical CollegeHenan Key Laboratory of Organic Functional Molecule and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal UniversityState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical CollegeGenuine Biotech. Inc.State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical CollegeInstitute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical CollegeGenuine Biotech. Inc.National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Science and Peking Union Medical CollegeSchool of Chemistry, Zhengzhou UniversityState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical CollegeInstitute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical CollegeDepartment of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan Research Center for Infectious Diseases and CancerHenan Key Laboratory of Organic Functional Molecule and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal UniversityState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical CollegeAbstract Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 μM, depending on viruses or cells, and selective index (SI) in 15–83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1–9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2–25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.https://doi.org/10.1038/s41392-021-00835-6 |
| spellingShingle | Jin-Lan Zhang Yu-Huan Li Lu-Lu Wang Hong-Qi Liu Shuai-Yao Lu Yong Liu Ke Li Bin Liu Su-Yun Li Feng-Min Shao Kun Wang Ning Sheng Rui Li Jin-Jin Cui Pei-Chun Sun Chun-Xia Ma Bo Zhu Zhe Wang Yuan-Hao Wan Shi-Shan Yu Yongsheng Che Chao-Yang Wang Chen Wang Qiangqian Zhang Li-Min Zhao Xiao-Zhong Peng Zhenshun Cheng Jun-Biao Chang Jian-Dong Jiang Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients Signal Transduction and Targeted Therapy |
| title | Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients |
| title_full | Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients |
| title_fullStr | Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients |
| title_full_unstemmed | Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients |
| title_short | Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients |
| title_sort | azvudine is a thymus homing anti sars cov 2 drug effective in treating covid 19 patients |
| url | https://doi.org/10.1038/s41392-021-00835-6 |
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