tetano
Editor, Senior Moderator
Signal Transduct Target Ther
. 2021 Dec 6;6(1):414.
doi: 10.1038/s41392-021-00835-6.
Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients
Jin-Lan Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Yu-Huan Li[SUP] #[/SUP][SUP] 2 [/SUP], Lu-Lu Wang[SUP] #[/SUP][SUP] 1 2 [/SUP], Hong-Qi Liu[SUP] #[/SUP][SUP] 3 [/SUP], Shuai-Yao Lu[SUP] #[/SUP][SUP] 3 [/SUP], Yong Liu[SUP] 4 [/SUP], Ke Li[SUP] 2 [/SUP], Bin Liu[SUP] 5 [/SUP], Su-Yun Li[SUP] 6 [/SUP], Feng-Min Shao[SUP] 7 [/SUP], Kun Wang[SUP] 2 [/SUP], Ning Sheng[SUP] 1 [/SUP], Rui Li[SUP] 1 [/SUP], Jin-Jin Cui[SUP] 2 [/SUP], Pei-Chun Sun[SUP] 7 [/SUP], Chun-Xia Ma[SUP] 3 [/SUP], Bo Zhu[SUP] 8 [/SUP], Zhe Wang[SUP] 1 [/SUP], Yuan-Hao Wan[SUP] 4 [/SUP], Shi-Shan Yu[SUP] 1 [/SUP], Yongsheng Che[SUP] 2 [/SUP], Chao-Yang Wang[SUP] 4 [/SUP], Chen Wang[SUP] 9 [/SUP], Qiangqian Zhang[SUP] 10 [/SUP], Li-Min Zhao[SUP] 1 [/SUP], Xiao-Zhong Peng[SUP] 11 [/SUP], Zhenshun Cheng[SUP] 12 [/SUP], Jun-Biao Chang[SUP] 13 14 [/SUP], Jian-Dong Jiang[SUP] 15 16 [/SUP]
Affiliations
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 EC[SUB]50[/SUB] 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.
. 2021 Dec 6;6(1):414.
doi: 10.1038/s41392-021-00835-6.
Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients
Jin-Lan Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Yu-Huan Li[SUP] #[/SUP][SUP] 2 [/SUP], Lu-Lu Wang[SUP] #[/SUP][SUP] 1 2 [/SUP], Hong-Qi Liu[SUP] #[/SUP][SUP] 3 [/SUP], Shuai-Yao Lu[SUP] #[/SUP][SUP] 3 [/SUP], Yong Liu[SUP] 4 [/SUP], Ke Li[SUP] 2 [/SUP], Bin Liu[SUP] 5 [/SUP], Su-Yun Li[SUP] 6 [/SUP], Feng-Min Shao[SUP] 7 [/SUP], Kun Wang[SUP] 2 [/SUP], Ning Sheng[SUP] 1 [/SUP], Rui Li[SUP] 1 [/SUP], Jin-Jin Cui[SUP] 2 [/SUP], Pei-Chun Sun[SUP] 7 [/SUP], Chun-Xia Ma[SUP] 3 [/SUP], Bo Zhu[SUP] 8 [/SUP], Zhe Wang[SUP] 1 [/SUP], Yuan-Hao Wan[SUP] 4 [/SUP], Shi-Shan Yu[SUP] 1 [/SUP], Yongsheng Che[SUP] 2 [/SUP], Chao-Yang Wang[SUP] 4 [/SUP], Chen Wang[SUP] 9 [/SUP], Qiangqian Zhang[SUP] 10 [/SUP], Li-Min Zhao[SUP] 1 [/SUP], Xiao-Zhong Peng[SUP] 11 [/SUP], Zhenshun Cheng[SUP] 12 [/SUP], Jun-Biao Chang[SUP] 13 14 [/SUP], Jian-Dong Jiang[SUP] 15 16 [/SUP]
Affiliations
- PMID: 34873151
- DOI: 10.1038/s41392-021-00835-6
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 EC[SUB]50[/SUB] 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.