药学学报, 2020, 55(6): 1073-1080
引用本文:
刘艾林, 杜冠华. 基于靶点的抗新型冠状病毒病COVID-19药物发现[J]. 药学学报, 2020, 55(6): 1073-1080.
LIU Ai-lin, DU Guan-hua. Drug discovery for COVID-19 treatment based on drug targets[J]. Acta Pharmaceutica Sinica, 2020, 55(6): 1073-1080.

基于靶点的抗新型冠状病毒病COVID-19药物发现
刘艾林, 杜冠华
中国医学科学院、北京协和医学院药物研究所, 北京 100050
摘要:
新型冠状病毒(SARS-CoV-2)引发的新冠病毒病(COVID-19),采取对症治疗不失为可行有效的治疗方案,但治疗药物大多缺乏针对性。基于病毒复制过程中的关键蛋白和病毒引发的病理机制,研制有针对性的治疗药物,将为临床提供更加有效的治疗方案。此外,由于新型冠状病毒是RNA病毒,而RNA病毒基因易于变异,因此针对新冠病毒病的新药研发将是一项长期而艰巨的任务。本文基于新型冠状病毒从吸附、进入宿主细胞到病毒复制过程中的关键蛋白及病毒感染引发的致病因素等多个环节的潜在靶点,利用分子模拟和机器学习等算法,探讨防治COVID-19新药发现的研究思路,并简述本课题组所开展的相关工作,为促进不同作用机制的新药发现提供可行性研究方法和策略。
关键词:    新型冠状病毒      新型冠状病毒病      药物靶点      药物发现      分子模拟      机器学习     
Drug discovery for COVID-19 treatment based on drug targets
LIU Ai-lin, DU Guan-hua
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus (SARS-CoV-2) is treated in accordance with symptoms, which is feasible and effective. However, current therapeutic drugs are ineffective against this virus. The development of targeted therapeutic drugs that are based on key proteins in SARS-CoV-2 replication and pathogenesis will provide a more effective means for clinical treatment. In addition, because SARS-CoV-2 is an RNA virus, which typically mutate readily, new drug development against COVID-19 will be a long-term and arduous task. New approaches to drug discovery for COVID-19 treatment using molecular simulation and machine learning algorithms, and based on the key proteins in the process of SARS-CoV-2 adsorption, entry into the host cell and viral replication are discussed herein, and we briefly introduce related work in our laboratory that can provide strategies to promote the discovery of drugs with different mechanisms of action.
Key words:    novel coronavirus    novel coronavirus disease    drug target    drug discovery    molecular simulation    machine learning   
收稿日期: 2020-03-13
DOI: 10.16438/j.0513-4870.2020-0319
基金项目: “十三五”重大新药创制专项(2018ZX09711001-003-002,2018ZX09711001-012);国家自然科学基金资助项目(81673480);协和创新工程项目(2016-I2M-3-007).
通讯作者: 刘艾林,Tel:86-10-83150885,E-mail:liuailin@imm.ac.cn;杜冠华,E-mail:dugh@imm.ac.cn
Email: liuailin@imm.ac.cn;dugh@imm.ac.cn
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