重组人干扰素α1b与新型冠状病毒肺炎防治

doi:10.13523/j.cb.2002107

中国生物工程杂志

2020, Vol. 40

Issue (1-2): 71-77 DOI: 10.13523/j.cb.2002107

冠状病毒药物研发与技术情报专辑

重组人干扰素α1b与新型冠状病毒肺炎防治

程永庆(

),刘金毅,林福玉,童梅

北京三元基因药业股份有限公司北京 102600

Novel Coronavirus Control and the Important Contribution of Interferon α1b

CHENG Yong-qing(

),LIU Jin-yi,LIN Fu-Yu,TONG Mei

Beijing Tri-Prime Gene Pharmaceutical Co., Ltd.,Beijing 102600,China

全文: PDF(510 KB) HTML

摘要：

干扰素调节免疫具有广谱抗病毒和抗肿瘤作用。重组人干扰素α1b是国内自主产权的基因工程I类新药,通过多年研究,研制出儿童和成人应用的重组人干扰素α1b注射液、喷雾剂等多种剂型,完成治疗冠状病毒等肺炎的药理学、毒理学、药代动力学和相关临床研究,形成了多个临床应用的专家共识和指南性文件。新型冠状病毒肺炎疫情发生后,这些研究为国家卫健委将干扰素α雾化吸入作为首推抗病毒药物试用方案纳入《新型冠状病毒感染的肺炎国家诊疗方案》提供了基础。经过大量新冠肺炎患者的临床使用,取得了良好的治疗效果。重组人干扰素α1b喷雾剂作为可预防病毒感染的药物,用于医护人员等高暴露人群的生物防护,为疫情防控发挥了重要作用,将对国民健康和国家生物安全保障做出应有的贡献。

关键词： 新型冠状病毒; 干扰素α; 雾化吸入

Abstract:

Interferon has broad-spectrum antiviral, immunomodulatory and antitumor effects. Recombinant human interferon α1b is the first class I genetic engineering new drug with independent intellectual property rights in China. After years of research, a variety of dosage forms such as recombinant human interferon α1b injections and sprays for children and adults have been developed. A series of pharmacological, toxicological, pharmacokinetic and clinical studies on interferon α1b for the treatment of pneumonia such as coronavirus have been completed, becoming clinical consensus and guidance documents. According to these results, interferon α aerosol inhalation was recommended as the first anti-viral treatment of novel coronavirus caused pneumonia in multi-version of "National diagnosis and treatment of novel coronavirus caused pneumonia" released by National Health Commission of the People's Republic of China, and achieved good medical effects. Recombinant human interferon α1b spray, as a drug that can prevent viral infections, is widely used in the biological protection of high-exposure populations such as medical personnel, which plays an important role in the prevention and control of the epidemic, and will make contributions to national health and biosafety.

Key words: Novel coronavirus Interferon α Pulverization inhalation

收稿日期: 2020-02-24 出版日期: 2020-03-27

ZTFLH:

Q819

通讯作者: 程永庆 E-mail: ycheng@triprime.com

	服务
	把本文推荐给朋友
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	程永庆
	刘金毅
	林福玉
	童梅

引用本文:

程永庆,刘金毅,林福玉,童梅. 重组人干扰素α1b与新型冠状病毒肺炎防治[J]. 中国生物工程杂志, 2020, 40(1-2): 71-77.

CHENG Yong-qing,LIU Jin-yi,LIN Fu-Yu,TONG Mei. Novel Coronavirus Control and the Important Contribution of Interferon α1b. China Biotechnology, 2020, 40(1-2): 71-77.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2002107 或 https://manu60.magtech.com.cn/biotech/CN/Y2020/V40/I1-2/71

表1 SARS-CoV-2、SARS-CoV、MERS-CoV的区别

[1]	Isaacs A, Lindenmann J . Virus interference. I. The interferon. Proc R Soc Lond Ser B Biol Sci, 1957,147(927):258-267.
[2]	Sidney P, Christopher D K, Mark R W , et al. Interferons, interferon-like cytokines, and their receptors. Immunol Rev, 2004,202:8-32.
[3]	Schoggins J W, Rice C M . Interferon-stimulated genes and their antiviral effector functions. Curr opin virol, 2011,1(6):519-525.
[4]	Mehta H V, Jones P H, Weiss J P , et al. IFN-α and lipopolysaccharide upregulate APOBEC3 mRNA through different signaling pathways. J Immunol, 2012,189(8):4088-4103.
[5]	David M . Signal transduction by type I interferons. Biotechniques, 2002,Suppl(2):58-65.
[6]	Lekmine F, Uddin S, Sassano A , et al. Activation of the p70 S6 kinase and phosphorylation of the 4E-BP1 repressor of mRNA translation by type I interferons. J Biol Chem, 2003,278(30):27772-27780.
[7]	Uematsu S, Akira S . Toll-like receptors and type I interferons. J Biol Chem, 2007,282(21):15319-15323.
[8]	侯云德, 张智清, 杨新科 , 等. 人白细胞干扰素基因的克隆化及其在大肠杆菌中的表达. 中国医学科学院学报, 1982,6:4-12.
	Hou Y D, Zhang Z Q, Yang X K , et al. Cloning of human leukocyte interferon gene and its expression in E. coli. Journal of the Chinese Academy of Medical Sciences, 1982,6:4-12.
[9]	北京三元基因工程有限公司. 一种稳定的重组人干扰素α1b水溶液:中国,CN200410069390.4.[2006-1-25]. http://pss-system.cnipa.gov.cn/sipopublicsearch.
	Beijing Tri-Prime Gene Pharmaceutical Co., Ltd.. A stable recombinant human interferon α1b aqueous solution: China, CN200410069390.4..[2006-1-25]. http://pss-system.cnipa.gov.cn/sipopublicsearch.
[10]	中华医学会临床药学分会, 雾化吸入疗法合理用药专家共识. 医药导报, 2019,38(2):135-146.
	Clinical Pharmacy Branch of Chinese Medical Association. Expert consensus on rational use of nebulized inhalation therapy. Medical Herald, 2019,38(2):135-146.
[11]	王雪, 陈韡亚, 杨飞飞 , 等. 重组人干扰素α1b注射液的雾化可吸入性研究. 国际药学研究杂志, 2019,46(6):456-460.
	Wang X, Chen Y Y, Yang F F , et al. Studies on nebulization respirability of recombinant human interferon α 1b. International Journal of Pharmaceutical Research, 2019,46(6):456-460.
[12]	刘鉴峰, 刘金剑, 褚丽萍 , 等. 雾化吸入干扰素α1b在兔体内的分布及代谢途径. 医药导报, 2013,32(1):1-5.
	Liu J F, Liu J J, Chu L P , et al. Distribution and metabolic pathways of aerosolized interferon α1b in rabbits. Medical Herald, 2013,32(1):1-5.
[13]	孙薇, 乔逸, 郭丽 , 等. 小儿注射重组人干扰素α1b 治疗病毒性肺炎的耐受性及安全性. 中国新药杂志, 2011,20(23):2340-2344.
	Sun W, Qiao Y, Guo L , et al. Tolerability and safety of pediatric injection of recombinant human interferon α1b in the treatment of viral pneumonia. Chinese Journal of New Drugs, 2011,20(23):2340-2344.
[14]	尚云晓, 黄英, 刘恩梅 , 等. 雾化吸入重组人干扰素α1b治疗小儿急性毛细支气管炎多中心研究. 中国实用儿科杂志, 2014,29(11):840-844.
	Shang Y X, Huang Y, Liu E M , et al. Multicenter study of nebulized inhaled recombinant human interferon α1b in the treatment of children with acute bronchitis. Chinese Journal of Practical Pediatrics, 2014,29(11):840-844.
[15]	Jiang R M, Han B, Song M H , et al. Randomized, double-blind, placebo-controlled, multicenter clinical study of recombinant human interferon α1b aerosol inhalation for noninfluenza viral pneumonia. Inflammation, 2020, accepsubmitted.
[16]	Zhu N, Zhang D, Wang W , et al. A novel coronavirus from patients with pneumonia in China. N Engl J Med. 2020 Jan 24. doi: 10.1056/NEJMoa2001017. doi: 10.1056/NEJMoa2001017
[17]	Zhou P, Yang X L, Wang X G , et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Feb 3. doi: 10.1038/s41586-020-2012-7. doi: 10.1038/s41586-020-2012-7
[18]	Lam T TY, Shum M HH, Zhu H C , et al. Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China. BioRxiv, 2020. doi. org/10.1101/2020.02.13.945985. doi: org/10.1101/2020.02.13.945985
[19]	Wu A, Peng Y, Huang B , et al. Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe, 2020, doi: 10.1016/j.chom.2020.02.001. doi: 10.1016/j.chom.2020.02.001
[20]	Yang Y, Lu Q B, Liu M J , et al. Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China. medRxiv, 2020, https://doi.org/10.1101/2020.02.10.20021675.
[21]	Kindler E, Thiel V . To sense or not to sense viral RNA--essentials of coronavirus innate immune evasion. Curr Opin Microbio, 2014,20:69-75.
[22]	Zhao L, Jha B K, Wu A , et al. Antagonism of the interferon-induced OAS-RNase L pathway by murine coronavirus ns2 protein is required for virus replication and liver pathology. Cell Host Microbe, 2012,11(6):607-616.
[23]	Hu Y, Li W, Gao T , et al. The severe acute respiratory syndrome coronavirus nucleocapsid inhibits type I interferon production by interfering with TRIM25-mediated RIG-I ubiquitination. J Virol, 2017,91(8):e02143-16.
[24]	Tumpey T M, Basler C F, Aguilar P V , et al. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science, 2005,310(5745):77-80.
[25]	Roberts A, Deming D, Paddock C D , et al. A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice. PLoS Pathog, 2007,3(1):e5.
[26]	孙莉, 刘殿波, 杨宇东 , 等. 人类冠状病毒调节宿主抗病毒天然免疫分子机制. 生物化学与生物物理进展, 2010,37(3):239-244.
	Sun L, Liu D B, Yang Y D , et al. Molecular mechanisms of human coronavirus regulating host-antiviral natural immunity. Advances in Biochemistry and Biophysics, 2010,37(3):239-244.
[27]	段招军, 张丽兰, 谢志萍 , 等. 不同型别重组人干扰素在细胞培养上抗SARS病毒的研究. 中华实验和临床病毒学杂志, 2003,17(3):205-208.
	Duan Z J, Zhang L L, Xie Z P , et al. Study on anti-SARS effects in cell culture of different types of recombinant human interferons. Chinese Journal of Experimental and Clinical Virology, 2003,17(3):205-208.
[28]	Barnard D L, Day C W, Bailey K , et al. Evaluation of immunomodulators, interferons and known in vitro SARS-coV inhibitors for inhibition of SARS-coV replication in BALB/c mice. Antivir Chem Chemoth, 2006,17(5):275-284.
[29]	Falzarano D, Wit E, Rasmussen A L , et al. Treatment with interferon-alpha 2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med, 2013,19(10):1313-1317.
[30]	郭利民, 刘景院, 蔡皓东 , 等. SARS的临床特点与治疗研究. 中国临床医生, 2003,31(1):17-20.
	Guo L M, Liu J Y, Cai H D , et al. Clinical characteristics and treatment of SARS. Chinese Clinician, 2003,31(1):17-20.
[31]	付琦, 李志刚, 马烈 , 等. SARS抗病毒治疗的药物选择探讨. 解放军药学学报, 2003,19(6):410-413.
	Fu Q, Li Z G, Ma L , et al. Discussion on drug selection for SARS antiviral therapy. Pharmacy Journal of the PLA, 2003,19(6):410-413.
[32]	付琦, 李杏红, 李志刚 . 抗病毒药物治疗严重急性呼吸道综合征时机的探讨. 中国药物与临床, 2003,3(5):389-391.
	Fu Q, Li X H, Li Z G . Discussion on the timing of antiviral drugs for severe acute respiratory syndrome. Chinese Medicine and Clinic, 2003,3(5):389-391.
[33]	刘冬生, 欧阳菊香, 邹敏超 , 等. 常用抗病毒药物对SARS疗效的多因素分析. 中华医院感染学杂志, 2009,19(4):434-436.
	Liu D S, Ouyang J X, Zou M C , et al. Multivariate analysis of the efficacy of commonly used antiviral drugs on SARS. Chinese Journal of Nosocomiology, 2009,19(4):434-436.
[34]	申昆玲, 张国成, 尚云晓 , 等. 重组人干扰素-α1b在儿科的临床应用专家共识. 中华实用儿科临床杂志, 2015,30(16):1214-1219.
	Shen K L, Zhang G C, Shang Y X , et al. Expert consensus on clinical application of recombinant human interferon-α1b in pediatrics. Chinese Journal of Practical Pediatrics, 2015,30(16):1214-1219.
[35]	申昆玲 . 儿童雾化中心规范化管理指南(第二版). 人民卫生出版社, 2016: 22.
	Shen K L. Guidelines for standardized management of children’s atomization centers, 2nd ed. People's Medical Publishing House, 2016: 22.
[36]	申昆玲, 尚云晓, 张国成 , 等. α干扰素在儿科临床合理应用专家共识. 中华实用儿科临床杂志, 2018,33(17):1301-1308.
	Shen K L, Shang Y X, Zhang G C , et al. Expert consensus on rational application of interferon alpha in pediatrics. Chinese Journal of Practical Pediatrics, 2018,33(17):1301-1308.
[37]	国家卫生计生委儿童用药专家委员会,中华医学会儿科学分会呼吸学组,中国医师协会儿科医师分会儿童呼吸专业委员会, 等. 儿童喘息性疾病合理用药指南. 中华实用儿科临床杂志, 2018,33(19):1460-1472.
	National Committee of Health and Family Planning, Committee on Child Medication, Respiratory Group of Pediatrics Branch of Chinese Medical Association, Child Respiratory Professional Committee of Pediatrician Branch of Chinese Medical Association, et al. Guidelines for the rational use of children’s asthmatic diseases. Chinese Journal of Practical Pediatrics, 2018,33(19):1460-1472.
[38]	中华医学会儿科学分会感染学组,国家感染性疾病医疗质量控制中心. 疱疹性咽峡炎诊断及治疗专家共识(2019年版). 中华儿科杂志, 2019,57(3):177-180.
	Department of Infectious Diseases, Pediatrics Branch of Chinese Medical Association, National Center for Medical Quality Control of Infectious Diseases. Expert consensus on diagnosis and treatment of herpes pharyngitis (2019 Edition). Chinese Journal of Pediatrics, 2019,57(3):177-180.
[39]	申昆玲, 王天有 . 临床路径释义-小儿内科分册. 北京: 中国协和医科大学出版社, 2018: 186.
	Shen K L, Wang T Y. Interpretation of Clinical Pathway-Pediatric Internal Medicine Volume. Beijing: Peking Union Medical College Press, 2018: 186.
[40]	Hayden F G, Mills S E, Johns M E . Human tolerance and histopathologic effects of long-term administration of intranasal interferon-alpha 2. J Infect Dis, 1983,148(5):914-921.
[41]	国琴, 李思思 . 重组人干扰素 α-1b 喷雾剂治疗儿童疱疹性咽峡炎疗效观察. 儿科药学杂志, 2019,25(2):31-33.
	Guo Q, Li S S . Observation of curative effect of recombinant human interferon α-1b spray on children with herpetic angina. Journal of Pediatric Pharmacy, 2019,25(2):31-33.
[42]	中华人民共和国国家卫生健康委员会. 新型冠状病毒感染的肺炎诊疗方案(试行第六版). 2020:7. [2020-03-02] https://xw.qq.com/cmsid/20200219A0H8TG00.
	National Health Committee of the People’s Republic of China. Diagnosis and treatment of pneumonitis with new coronavirus infection,6th ed. 2020:7. [2020-03-02] https://xw.qq.com/cmsid/20200219A0H8TG00.

[1]	贠涛,巩玥,谷芃,徐冰冰,李瑾,赵洗尘. 中国与“一带一路”参与国家抗击新冠肺炎疫情的国际科技合作现状与展望[J]. 中国生物工程杂志, 2021, 41(7): 110-121.
[2]	史瑞,严景华. 抗新型冠状病毒单克隆中和抗体药物研发进展^*[J]. 中国生物工程杂志, 2021, 41(6): 129-135.
[3]	张赛,王刚,刘仲明,李辉军,汪大明,钱纯亘. 新型冠状病毒胶体金抗原快速检测试剂的研制及性能评价^*[J]. 中国生物工程杂志, 2021, 41(5): 27-34.
[4]	范月蕾,王跃,王恒哲,李丹丹,毛开云. 新型冠状病毒体外诊断技术研发现状与展望 ^*[J]. 中国生物工程杂志, 2021, 41(2/3): 150-161.
[5]	张赛,向乐,李林海,李辉军,王刚,钱纯亘. 新型冠状病毒(2019-nCoV)IgM /IgG抗体检测试剂的研制及性能评价[J]. 中国生物工程杂志, 2020, 40(8): 1-9.
[6]	林福玉,刘金毅,程永庆. 重组人干扰素α1b抗新型冠状病毒的基础和临床研究进展[J]. 中国生物工程杂志, 2020, 40(12): 1-7.
[7]	王国强,于茵茵,曾华辉,王旭东,吴玉彬,尚立芝,李玉林,张怡青,张西西,张振强,王云龙. 基于MS2噬菌体病毒样颗粒的RT-PCR检测新型冠状病毒(SARS-CoV-2)质控品制备^*[J]. 中国生物工程杂志, 2020, 40(12): 31-40.
[8]	陈利军,屈晶晶,项春生. 间充质干细胞在2019新型冠状病毒肺炎(COVID-19)中的治疗潜能、临床研究与应用前景^*[J]. 中国生物工程杂志, 2020, 40(11): 43-55.
[9]	赵广荣梁玲玲刘春杰祝琳琪. 邻近多位点基因突变的组合大引物PCR策略[J]. 中国生物工程杂志, 2010, 30(07): 0-0.

Viewed

Full text

Abstract

Cited

Shared

Discussed