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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

Signal transduction and targeted therapy, 2021-12, Vol.6 (1), p.414-414, Article 414 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients
Autor: 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
Assuntos: Adult ; Aged ; Aged, 80 and over ; Animals ; Antiviral Agents - administration & dosage ; Azides - administration & dosage ; Cell migration ; Coronavirus OC43, Human - metabolism ; Coronaviruses ; COVID-19 ; COVID-19 Drug Treatment ; Deoxycytidine - administration & dosage ; Deoxycytidine - analogs & derivatives ; DNA-directed RNA polymerase ; Female ; HIV ; Human immunodeficiency virus ; Humans ; Leukocytes (mononuclear) ; Lymphocytes ; Male ; Middle Aged ; Nausea ; Nucleoside analogs ; Oral administration ; Patients ; Peripheral blood mononuclear cells ; Rats ; RNA polymerase ; RNA-directed RNA polymerase ; SARS-CoV-2 - metabolism ; Severe acute respiratory syndrome coronavirus 2 ; Thymus ; Thymus gland ; Thymus Gland - metabolism ; Thymus Gland - virology
É parte de: Signal transduction and targeted therapy, 2021-12, Vol.6 (1), p.414-414, Article 414
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SourceType-Scholarly Journals-1
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Descrição: 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 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.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients

England: Nature Publishing Group

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