溴己新治疗新型冠状病毒肺炎的潜在机制分析  

Potential Mechanistic Investigation of Bromhexine for the Treatment of COVID-19

作　　者：杨勇 沈浩 赵山美子 王东[4] 王浩然 YANG Yong;SHEN Hao;ZHAO Shan-mei-zi;WANG Dong;WANG Hao-ran(Personalized Drug Therapy Key Laboratory of Sichuan Province,Department of Pharmacy,Sichuan Academy of Medical Sciences&Sichuan Provincial People's Hospital,Chengdu 610072,China;School of Medicine,University of Electronic Science and Technology of China,Chengdu 611731,China;Guangzhou Institute of Pediatrics,Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University,Guangzhou 510623,China;School of Traditional Chinese Materia Medica,Shenyang Pharmaceutical University,Shenyang 110016,China;Neoland Biosciences,Weihai 264200,China)

机构地区：[1]四川省医学科学院,四川省人民医院药学部,个体化药物治疗四川省重点实验室,成都610072 [2]电子科技大学医学院,成都611731 [3]广州医科大学附属广州市妇女儿童医疗中心儿科研究所,广州510623 [4]沈阳药科大学中药学院,沈阳110016 [5]纽兰生物科技有限公司,山东威海264200

出　　处：《中国药学杂志》2020年第9期679-684,共6页Chinese Pharmaceutical Journal

基　　金：国家临床重点专科建设项目资助(30305030698);四川省省级公益性科研院所基本科研业务专项课题项目资助(2018YSKY0017);四川省人民医院院级科研基金临床研究及转化项目资助(2018LY09)。

摘　　要：目的2019年12月新型冠状病毒肺炎(COVID-19)暴发,疫情在世界范围内迅速蔓延,寻找有效抗病毒药物成为治疗新型冠状病毒的迫切需求。方法笔者借助已有病毒学文献,对严重急性呼吸系统综合征冠状病毒2(SARS-CoV-2)感染通路进行了系统的总结,并且运用SWISSDOCK分子模拟方法对关键靶点和上市药物进行系统的虚拟药物筛选。结果研究发现,TMPRSS2/ACE2通路是SARS-CoV-2病毒进入肺部和其他组织细胞最高效和主要的途径。而呼吸科祛痰药物溴己新体外可强烈抑制TMPRSS2蛋白酶(EC50:0.75μmol·L^-1)。溴己新不良反应少且还具备促进肺部内源活性物质释放,维持肺泡功能,促进排痰等有益作用,适合联合用药。结论溴己新具有独特的潜在抗病毒机制,应当深入进行临床研究,发挥其对COVID-19预防,治疗和预后的作用。OBJECTIVE To investigate antiviral mechanism of bromhexine for the treatment of COVID-19.METHODS Based on the existing literature,the infection pathways of new coronavirus(SARS-CoV-2)were systematically summarized by us,and used the SWISSDOCK molecular simulation method to carry out virtual screen systematically for key targets and marketed drugs.RESULTS TMPRSS2/ACE2 pathway was found to be the most efficient and probably the major pathway for SARS-CoV-2 virus to infect the lung and other tissue by us.Bromhexine,an expectorant,can strongly inhibit TMPRSS2 protease(EC50:0.75μmol·L^-1)in vitro.Bromhexine has few adverse effects and also has the beneficial effects of promoting the release and maintenance of endogenous active substances in the lung,alveolar function,and promoting sputum excretion,which is suitable for use together with other COVID19 medication and therapies.CONCLUSION Bromhexine has a unique potential antiviral mechanism,and clinical research should be conducted to play its role in the prevention,treatment and prognosis of COVID19.

关 键 词：溴己新 氯喹 新型冠状病毒肺炎 严重急性呼吸系统综合征冠状病毒2 抗病毒机制 

分 类 号：R9[医药卫生—药学]