Background
Azvudine hydrochloride is a potent nucleoside reverse transcriptase inhibitor (NRTI) that has antiviral activity against HIV, HBV, and HCV,(HIV-1 (EC50s 0.03 to 6.92 nM) and HIV-2 (EC50s 0.018 to 0.025 nM))[1]. Azivudine hydrochloride could inhibit SARS-CoV-2 and HCoV-OC43 coronavirus with EC50 1.2-4.3 μM[3].
In C8166 cells,Azvudine hydrochloride showed strong inhibition against wild-type HIV-1 IIIB and HIV-1 RF, with 50% effective concentration values (EC 50) ranging from 30 to 110 pM[2].
EV71 and CA16 challenge resulted in 90% and 30% mortality, respectively, while Azvudine hydrochloride treatment greatly reduced mortality to 20% and 0%. Azvudine hydrochloride treatment significantly improved clinical presentation and survival, indicating that Azvudine hydrochloride effectively protects against EV71 and CA16 challenge in vivo[4].
Treating SARS-CoV-2 infected rhesus macaques with Azvudine hydrochloride (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[3].
Azvudine hydrochloride clinical efficacy in curing COVID-19 was significant, showing inhibition of SARS-CoV-2 replication in all 31 patients after treatment with Azvudine hydrochloride, and the anti-coronavirus activity of Azvudine hydrochloride was also demonstrated in animal experiments using RM[5].
参考文献:
[1]: Wang RR, Yang QH, et,al. Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. PLoS One. 2014 Aug 21;9(8):e105617. doi: 10.1371/journal.pone.0105617. PMID: 25144636; PMCID: PMC4140803.
[2]: Zhou Y, Zhang Y, et,al.Novel nucleoside analogue FNC is effective against both wild-type and lamivudine-resistant HBV clinical isolates. Antivir Ther. 2012;17(8):1593-9. doi: 10.3851/IMP2292. Epub 2012 Aug 9. PMID: 22910281.
[3]: Zhang JL, Li YH, et,al. Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients. Signal Transduct Target Ther. 2021 Dec 6;6(1):414. doi: 10.1038/s41392-021-00835-6. PMID: 34873151; PMCID: PMC8646019.
[4]: Xu N, Yang J, et,al.The Pyrimidine Analog FNC Potently Inhibits the Replication of Multiple Enteroviruses. J Virol. 2020 Apr 16;94(9):e00204-20. doi: 10.1128/JVI.00204-20. PMID: 32075935; PMCID: PMC7163137.
[5]: Ren Z, Luo H, et,al. A Randomized, Open-Label, Controlled Clinical Trial of Azvudine Tablets in the Treatment of Mild and Common COVID-19, a Pilot Study. Adv Sci (Weinh). 2020 Aug 13;7(19):2001435. doi: 10.1002/advs.202001435. PMID: 32837847; PMCID: PMC7404576.
[6]: Fayzullina D, Kharwar RK, et,al. FNC: An Advanced Anticancer Therapeutic or Just an Underdog? Front Oncol. 2022 Feb 10;12:820647. doi: 10.3389/fonc.2022.820647. PMID: 35223502; PMCID: PMC8867032.
Azvudine hydrochloride 是一种有效的核苷逆转录酶抑制剂 (NRTI)，对 HIV、HBV 和 HCV（HIV-1（EC50 0.03 至 6.92 nM）和 HIV-2（EC50 0.018 至 0.025 nM））具有抗病毒活性[1]。盐酸阿齐夫定对SARS-CoV-2和HCoV-OC43冠状病毒具有抑制作用，EC50为1.2-4.3 μM[3]。
在 C8166 细胞中，盐酸阿兹夫定对野生型 HIV-1 IIIB 和 HIV-1 RF 表现出强烈的抑制作用，50% 有效浓度值 (EC 50) 范围为 30 至 110 pM[2].
EV71 和 CA16 攻击分别导致 90% 和 30% 的死亡率，而盐酸阿兹夫定处理将死亡率大大降低至 20% 和 0%。阿兹夫定盐酸盐治疗显着改善了临床表现和生存率，表明阿兹夫定盐酸盐可有效保护体内免受 EV71 和 CA16 攻击[4]。
用盐酸阿兹夫定（0.07 毫克/千克，每日一次，口服）治疗感染 SARS-CoV-2 的恒河猴，可降低病毒载量，恢复胸腺，改善淋巴细胞分布，减轻炎症和器官损伤，并减轻毛玻璃样混浊胸部 X 光片[3].
盐酸阿兹夫定治疗 COVID-19 的临床疗效显着，在所有 31 名接受盐酸阿兹夫定治疗后的患者中均表现出抑制 SARS-CoV-2 复制的作用，并且在动物实验中也证明了盐酸阿兹夫定的抗冠状病毒活性RM[5].
Protocol
| Cell experiment [1]: |
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Cell lines
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C8166 cells
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Preparation Method
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Cells were seeded each well in a 96-well plate with Azvudine hydrochloride . The plate was placed in a humidified incubator. After incubation of 3-7 days, the percentage inhibition of syncytia formation was scored or the level of p24 was measured by ELISA and 50% effective concentration (EC50) were calculated.
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Reaction Conditions
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2nM Azvudine hydrochloride for 3-7 days at 37°C
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Applications
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Azvudine hydrochloride showed strong inhibition against wild-type HIV-1 IIIB and HIV-1 RF, with 50% effective concentration values (EC 50) ranging from 30 to 110 pM.
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| Animal experiment [2]: |
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Animal models
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Lethal EV71 and CA16 infection in neonatal mouse models
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Preparation Method
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The neonatal mice were randomly divided into five groups, and each group contained three litters . One group was inoculated intracerebrally with DMEM (10 μl/mouse) and after 1 h injected intraperitoneally with DMSO. Two groups were inoculated intracerebrally with EV71 CC063 and after 1 h injected intraperitoneally with Azvudine hydrochloride or DMSO. Azvudine hydrochloride was injected intraperitoneally on days 1, 3, 6, 9, and 12
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Dosage form
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1 mg/kg Azvudine hydrochloride on days 1, 3, 6, 9, and 12
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Applications
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EV71 and CA16 challenge resulted in 90% and 30% mortality, respectively, while Azvudine hydrochloride Azvudine hydrochloride treatment greatly reduced mortality to 20% and 0%. Azvudine hydrochloride treatment significantly improved clinical presentation and survival, indicating that FNC effectively protects against EV71 and CA16 challenge in vivo.
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参考文献:
[1]. Wang RR, Yang QH,et,al. Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro. PLoS One. 2014 Aug 21;9(8):e105617. doi: 10.1371/journal.pone.0105617. PMID: 25144636; PMCID: PMC4140803.
[2]. Xu N, Yang J, et,al.The Pyrimidine Analog FNC Potently Inhibits the Replication of Multiple Enteroviruses. J Virol. 2020 Apr 16;94(9):e00204-20. doi: 10.1128/JVI.00204-20. PMID: 32075935; PMCID: PMC7163137.
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