药学学报, 2020, 55(2): 181-188
引用本文:
刘千勇, 王晓良. 新型冠状病毒(2019-nCoV)的靶向药物研究策略[J]. 药学学报, 2020, 55(2): 181-188.
LIU Qian-yong, WANG Xiao-liang. Strategies for the development of drugs targeting novel coronavirus 2019-nCoV[J]. Acta Pharmaceutica Sinica, 2020, 55(2): 181-188.

新型冠状病毒(2019-nCoV)的靶向药物研究策略
刘千勇1, 王晓良2
1. 大有华夏生物医药集团有限公司, 北京100006;
2. 中国医学科学院药物研究所, 北京100050
摘要:
新型冠状病毒尚无特效药。新型冠状病毒靶向药物研发面临诸多挑战,其药物研发策略包括筛选广谱抗病毒药,老药新用,以及开发特异的全新药。药物既可抑制病毒靶点(如蛋白酶、合成酶、树突蛋白及病毒壳膜),又可靶向宿主(如病毒受体抑制剂、病毒内吞和跨膜蛋白酶抑制剂等)。最近核糖核酸合成酶抑制剂瑞德西韦在孤例重症患者表现出良好疗效,广谱病毒蛋白酶抑制剂克力芝也在临床上应用。这两种药刚启动III期临床试验,以评价其安全性和有效性。多种药物联用也是当前针对新型冠状病毒的一个主要策略,但应遵从科学依据和临床需求。通过大量文献和多种数据库检索,针对病毒和宿主细胞的关键成药靶点,作者挑选出75个临床在研的靶向药物,包括20个上市药,以助力临床前、临床试验研究和药物改良。
关键词:    新型冠状病毒      新型冠状病毒肺炎      靶向治疗      联合用药      瑞德西韦      克力芝     
Strategies for the development of drugs targeting novel coronavirus 2019-nCoV
LIU Qian-yong1, WANG Xiao-liang2
1. Tayu Huaxia Biotech Medical Group Co., Ltd., Beijing 100006, China;
2. Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China
Abstract:
There is no specific drug that has been approved for 2019-nCoV. There are a number of factors that pose major challenges in their development. Approaches to the development of anti-2019-nCoV include screening existing broad-spectrum antiviral drugs, repositioning of readily available clinical compounds, and de novo development of novel and specific agents for 2019-nCoV. Candidate compounds can be developed either to inhibit virus-based targets, such as RNA proteases, polymerase, spike glycoproteins, and viral envelop and membrane proteins, or to inhibit host-based targets, such as receptors and proteases that are utilized by virus for viral entry and endocytosis. Recently, the RNA polymerase remdesivir had demonstrated clinical efficacy in one patient with severe novel coronavirus pneumonia (NCP). The broad-spectrum viral protease inhibitor Kaletra® is also recommended in the current NCP clinical practice. Both drugs had lately been proceeded into multiple controlled phase III clinical trials to test their safety and efficacy in NCP. Combinational therapies consisting of multiple drugs provide other viable options against 2019-nCoV, based on scientific and clinical rationales. Using bioinformatics and database analysis, we have identified 75 clinically compounds, including 20 marketed compounds, that are efficacious in inhibiting key targets in virus- and host-based approaches, which may facilitate the development of new therapeutic options for 2019-nCoV.
Key words:    novel coronavirus 2019-nCoV    novel coronavirus pneumonia    targeted therapy    combination therapy    remdesivir    Kaletra   
收稿日期: 2020-02-09
DOI: 10.16438/j.0513-4870.2020-0106
通讯作者: 刘千勇,Tel:19901496030,E-mail:liuqianyong11@163.com;王晓良,Tel:13701166880,E-mail:wangxl@imm.ac.cn
Email: liuqianyong11@163.com;wangxl@imm.ac.cn
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