抗新型冠状病毒2019-nCoV新药的研发

doi:10.12092/j.issn.1009-2501.2020.03.001

摘要/Abstract

摘要： 2019年底，湖北武汉暴发了2019新型冠状病毒感染疾病（COVID-19），并快速在全国蔓延，且在多个国家发现病例。其感染病例和死亡病例在短时间内快速超过重症急性呼吸综合征（SARS），给中国带来了不可估量的损失。中国科研人员在短时间内，快速锁定病原体为2019-nCoV（或hCoV-19或SARS-CoV-2)，并且在不同层面开展了相关抗病毒药物的研发工作。本文介绍了抗2019-nCoV新药研发的现状。同时，鉴于突发病原体的药物研发过程相对迟缓，我们建议对于潜在流行可能性的病原体，其药物研发要具有前瞻性，国家层面要推进广谱药物的研发和临床试验，以应对可能出现的疫情风险。

关键词: 新型冠状病毒, 2019-nCoV, hCoV-19, SARS-CoV-2, 药物研发, 广谱

Abstract: At the end of 2019,an outbreak of 2019 new coronavirus infectious disease (COVID-19) in Wuhan spread rapidly in China and reported cases in other countries.The number of infected cases and deaths quickly exceeded Severe Acute Respiratory Syndrome (SARS) in a short period of time,resulting in incalculable losses to China.Chinese researchers have quickly identified the pathogen,2019-nCoV (or SARS-CoV-2 or HCoV-19) and carried out the research and development of antiviral drugs at different levels.This article briefly reviews the current advancement of research and development of new therapeutics against 2019-nCoV infection.Given that the progress of research and development of antiviral drugs against the emerging and reemerging pathogens is relatively backwarded,we suggest that the research and development of antivirals against pathogens with pandemic or epidemic potential should be carried out in advance before the occurrence of the outbreaks. At the national level,we should promote the research and development of broad-spectrum antivirals and clinical trials to combat the pathogens with epidemic risk.

Key words: new coronavirus, 2019-nCoV, hCoV-19, SARS-CoV-2, drug research and development, broad spectrum

中图分类号:

R511

刘奇，夏帅，姜世勃. 抗新型冠状病毒2019-nCoV新药的研发[J]. 中国临床药理学与治疗学, doi: 10.12092/j.issn.1009-2501.2020.03.001.

LIU Qi, XIA Shuai, JIANG Shibo. Research and development of antiviral drugs against new coronavirus 2019-nCoV[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, doi: 10.12092/j.issn.1009-2501.2020.03.001.

参考文献

［1］Gorbalenya AE,Baker SC,Baric RS,et al.Severe acute respiratory syndrome-related coronavirus:The species and its viruses-a statement of the Coronavirus Study Group［J/OL］.BioRxiv,2020.DOI:https://doi.org/10.1101/2020.02.07.937862.
［2］WHO.WHO Director-General'sremarks at the media briefing on 2019-nCoV on 11 February 20202020［EB/OL］.https://www.who.int/dg/speeches/detail/who-director-general-s-remarks-at-the-media-briefing-on-2019-ncov-on-11-february-2020.
［3］Jiang S,Shi Z,Shu Y,et al.A distinct name is needed for the new coronavirus emerged in Wuhan［J/OL］.Lancet,2020.https://doi.org/10.1016/S0140-6736(20)30419-0.
［4］李新华，高福.新型冠状病毒感染的肺炎公众防护指南［M］.北京:人民卫生出版社,2020.
［5］新华网.新型冠状病毒感染的肺炎疫情实时动态［EB/OL］.2020.http://fms.news.cn/swf/2020_sjxw/2_1_xgyq/index.html
［6］Zhou P,Yang X,Wang X,et al.A pneumonia outbreak associated with a new coronavirus of probable bat origin［J/OL］.Nature,2020.DOI: https://doi.org/10.1038/s41586-020-2012-7.
［7］Lu R,Zhao X,Li J,et al.Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding［J/OL］.Lancet,2020.DOI: https://doi.org/10.1016/S0140-6736(20)30251-8.
［8］中国科学院上海药物研究所.中国科学院上海药物研究所和上海科技大学联合研究团队发现一批可能对新型肺炎有治疗作用的老药和中药［EB/OL］.2020.http://www.simm.cas.cn/xwzx/kydt/202001/t20200125_5494417.html.
［9］华中科技大学.华中科技大学沈阳药科大学军事医学研究院联合发现可能用于治疗新冠肺炎的药物［J/OL］.2020.http://news.hust.edu.cn/info/1002/37436.htm.
［10］Du L,Yang Y,Zhou Y,et al.MERS-CoV spike protein:a key target for antivirals［J］.Expert Opin Ther Targets,2017,21(2):131-143.
［11］Zhou Y,Yang Y,Huang J,et al.Advances in MERS-CoV vaccines and therapeutics based on the receptor-binding domain［J］.Viruses,2019,11(1).DOI: 10.3390/v11010060.
［12］Tian X,Li C,Huang A,et al.Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody［J/OL］.2020. https://www.biorxiv.org/content/10.1101/2020.01.28.923011v1.
［13］澎湃新闻.北大团队：咳嗽药水沐舒坦具备治疗新型冠状病毒潜力［EB/OL］.2020.http://finance.sina.com.cn/china/2020-01-29/doc-iihnzhha5185162.shtml.
［14］天津国际生物医药联合研究院.联合研究院与南开大学药学院团队发现可预防冠状病毒感染作用的候选分子［EB/OL］.2020.http://www.tjab.org/Content.aspx?ArticleId=02e98c2a-76aa-423c-a8f1-f7d3c6c9dba1.
［15］Liu S,Xiao G,Chen Y,et al.Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: Implications for virus fusogenic mechanism and identification of fusion inhibitors［J］.2004,Lancet,363(9413):938-947.
［16］Lu L,Liu Q,Zhu Y,et al.Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor［J］.Nat Commun,2014,5:3067.
［17］Xia S,Yan L,Xu W,et al.A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike［J］.Sci Adv,2019,5(4):v4580.
［18］Xia S,Zhu Y,Liu M,et al.Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein［J/OL］. Cell Mol Immunol,2020. DOI: https://doi.org/10.1038/s41423-020-0374-2.
［19］Xia S,Liu M,Wang C,et al.Inhibiting SARS-CoV-2 infection by a highly potent pan-coronavirus fusion inhibitor targeting S protein with high capacity to mediate membrane fusion［J］.Cell Res,2020.accepted.
［20］Li BJ,Tang Q,Cheng D,et al.Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque［J］.Nat Med,2005,11(9):944-951.
［21］Tang Q,Li B Woodle M,et al.Application of siRNA against SARS in the rhesus macaque model［J］.Methods Mol Biol,2008,442:139-158.
［22］Nur SM,Hasan MA,Amin MA,et al.Design of potential RNAi (miRNA and siRNA) molecules for middle east respiratory syndrome coronavirus (MERS-CoV) gene silencing by computational method［J］.Interdiscip Sci,2015,7(3):257-265.
［23］蓝巧帅，夏帅，周洁，等.新型冠状病毒SARS-CoV-2感染治疗中的“老药新用”［J］.中国临床药理学与治疗学,2020,25(2):126-134.
［24］Xinhuanet.WHO enlists"Disease X"among most dangerous epidemics［EB/OL］.2018.http://www.xinhuanet.com/english/2018-03/12/c_137034109.htm.
［25］Jiang S,Lin K,Strick N,et al.HIV-1 inhibition by a peptide［J］.Nature,1993,365(6442):113.
［26］Yu Y,Deng Y,Zou P,et al.A peptide-based viral inactivator inhibits Zika virus infection in pregnant mice and fetuses［J］.Nat Commun,2017,8:15672.

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