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Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients.
Zhang, Jin-Lan; Li, Yu-Huan; Wang, Lu-Lu; Liu, Hong-Qi; Lu, Shuai-Yao; Liu, Yong; Li, Ke; Liu, Bin; Li, Su-Yun; Shao, Feng-Min; Wang, Kun; Sheng, Ning; Li, Rui; Cui, Jin-Jin; Sun, Pei-Chun; Ma, Chun-Xia; Zhu, Bo; Wang, Zhe; Wan, Yuan-Hao; Yu, Shi-Shan; Che, Yongsheng; Wang, Chao-Yang; Wang, Chen; Zhang, Qiangqian; Zhao, Li-Min; Peng, Xiao-Zhong; Cheng, Zhenshun; Chang, Jun-Biao; Jiang, Jian-Dong.
  • Zhang JL; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
  • Li YH; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
  • Wang LL; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
  • Liu HQ; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
  • Lu SY; Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Kunming, 650031, Yunnan, China.
  • Liu Y; Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Kunming, 650031, Yunnan, China.
  • Li K; Genuine Biotech. Inc., Pingdingshan, 467000, Henan, China.
  • Liu B; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
  • Li SY; Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan Research Center for Infectious Diseases and Cancer, Wuhan, 430071, Hubei, China.
  • Shao FM; The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, Henan, China.
  • Wang K; Department of Internal Medicine, Henan Provincial Peoples Hospital, Zhengzhou, 450003, Henan, China.
  • Sheng N; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
  • Li R; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
  • Cui JJ; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
  • Sun PC; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
  • Ma CX; Department of Internal Medicine, Henan Provincial Peoples Hospital, Zhengzhou, 450003, Henan, China.
  • Zhu B; Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Kunming, 650031, Yunnan, China.
  • Wang Z; Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453007, Henan, China.
  • Wan YH; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
  • Yu SS; Genuine Biotech. Inc., Pingdingshan, 467000, Henan, China.
  • Che Y; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
  • Wang CY; Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
  • Wang C; Genuine Biotech. Inc., Pingdingshan, 467000, Henan, China.
  • Zhang Q; National Clinical Research Center for Respiratory Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100005, China.
  • Zhao LM; School of Chemistry, Zhengzhou University, Zhengzhou, 450001, Henan, China.
  • Peng XZ; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
  • Cheng Z; Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Kunming, 650031, Yunnan, China. pengxiaozhong@pumc.edu.cn.
  • Chang JB; Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan Research Center for Infectious Diseases and Cancer, Wuhan, 430071, Hubei, China. chzs1990@163.com.
  • Jiang JD; Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453007, Henan, China. changjunbiao@zzu.edu.cn.
Signal Transduct Target Ther ; 6(1): 414, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1556321
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Azides / Thymus Gland / Deoxycytidine / SARS-CoV-2 / COVID-19 Type of study: Controlled clinical trial / Randomized controlled trials Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged Language: English Journal: Signal Transduct Target Ther Year: 2021 Document Type: Article Affiliation country: S41392-021-00835-6

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Azides / Thymus Gland / Deoxycytidine / SARS-CoV-2 / COVID-19 Type of study: Controlled clinical trial / Randomized controlled trials Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged Language: English Journal: Signal Transduct Target Ther Year: 2021 Document Type: Article Affiliation country: S41392-021-00835-6