新型冠状病毒——从基础研究到临床  

A novel coronavirus——from basic research to clinic

作　　者：罗丹 王霆 谭忠元 郭珊[2] 余志 刘艳[1] 张源 王宝香[2] 高源[2] 王汉中[1] 梅红[2] 郑振华[1] LUO Dan;WANG Ting;TAN ZhongYuan;GUO Shan;YU Zhi;LIU Yan;ZHANG Yuan;WANG BaoXiang;GAO Yuan;WANG HanZhong;MEI Hong;ZHENG ZhenHua(CAS Key Laboratory of Special Pathogens and Biosafety,Center for Emerging Infectious Diseases,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan 430071,China;Gastroenterology Department,Wuhan Children’s Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430015,China)

机构地区：[1]中国科学院武汉病毒研究所新发传染病研究中心,中国科学院高致病性病原生物学与生物安全重点实验室,武汉430071 [2]华中科技大学同济医学院附属武汉儿童医院消化科,武汉430015

出　　处：《中国科学：生命科学》2021年第11期1508-1522,共15页Scientia Sinica(Vitae)

基　　金：湖北省新冠肺炎应急科技项目(批准号:2020FCA004);中国科学院青年创新促进会(批准号:2016302)资助。

摘　　要：新型冠状病毒——严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARSCoV-2)席卷全球,已成为一个深刻改变人类世界的全球公共卫生问题.SARS-CoV-2基因组长度约为3万个碱基,编码16个非结构蛋白和4个结构蛋白.SARS-CoV-2的刺突(spike,S)蛋白S1亚基中的受体结合域(receptor-binding domain,RBD)与宿主肺泡Ⅱ型上皮细胞的受体血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2)结合;随之,S2亚基构型变化,介导病毒-宿主细胞之间的融合.依赖RNA的RNA聚合酶(RNA-dependent RNA polymerase,RdRp)对病毒基因组的复制至关重要.到2020年12月,全球共有7千多万确诊病例,死亡人数已超过160万.SARS-CoV-2可能源自蝙蝠,通过呼吸道飞沫和接触传播.感染后ACE2下调,并引发细胞因子风暴,导致肺部炎症及多器官损伤.SARS-CoV-2感染的常见症状包括发热、干咳、呼吸困难、疲劳和肌痛等,即新冠肺炎(coronavirus disease-2019,COVID-19).肺部影像学表现多为靠近胸膜的多发磨玻璃影和亚节段性实变.SARS-CoV-2可以通过病毒核酸、血清抗体、病毒分离和电子显微镜检测和观察.COVID-19病理改变为弥漫性肺泡损伤、纤维黏液样渗出物、间质炎症、肺泡上皮细胞增生和脱落以及透明膜形成.目前,临床上使用的抗病毒药物是非特异性的,主要有洛匹那韦/利托那韦、瑞德西韦、阿比多尔.EK1肽和SARS-CoV-2-HR2P是具有前景的新型抗病毒药物.恢复期血浆通常是一个有效的治疗选择.虽然目前尚无疫苗正式上市,但灭活疫苗、载体疫苗和核酸疫苗正进行临床试验.疫情出现后,中国迅速采取强有力的措施成功阻断了COVID-19在本土的传播.The pandemic of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) is now sweeping the globe like the toppling Dominoes,and has become an alarming public health issue worldwide.To date,there have been more than 76 million confirmed cases and more than 1,690,000 deaths worldwide.SARS-Co V-2 might originate from bats and is usually transmitted through respiratory droplets and contact.The SARS-Co V-2 genome is about 30 kilobases in length,encoding 16 non-structural proteins and 4 structural proteins.The receptor-binding domain(RBD) in the S1 subunit of the spike(S) protein of SARS-Co V-2 interacts with the entry receptor angiotensin-converting enzyme 2(ACE2) on host alveolar type II epithelial cells.The interaction causes structural changes in the S2 subunit leading to virus-host cell fusion.RNA-dependent RNA polymerase(Rd Rp) is vital to replication of the viral genome.ACE2 may be downregulated after infection,leading to lung edema and injury.Common symptoms of SARS-Co V-2 infection include fever,dry cough,dyspnea,fatigue,and myalgia,that is,a pneumonia that has been termed coronavirus disease-2019(COVID-19) by the World Health Organization.COVID-19 can be fatal.The imaging findings of the lung are mostly multiple ground glass shadows and subsegmental consolidation near the pleura.SARS-Co V-2 can be detected by nucleic acid and antibody tests,virus isolation,and electron microscopy.The pathological features of COVID-19 are diffuse alveolar injury,fibrous myxoid exudate,interstitial inflammation,alveolar epithelial cell proliferation and shedding,and hyaline membrane formation.At present,antivirals are non-specific and mainly include lopinavir/ritonavir,remdesivir,and umifenovir.EK1 peptide and SARS-Co V-2-HR2 P may be novel antiviral agents that can prevent infection.Convalescent plasma is generally a valid option.Although no vaccine is officially available,there are inactivated vaccines,vectored vaccines and nucleic acid-based vaccines in clinical trials.Prompt and strong measures have been taken to prev

关 键 词：SARS-CoV-2 COVID-19 分子特点 致病机制 抗病毒药物 

分 类 号：R373[医药卫生—病原生物学]