病毒3CL蛋白酶三维结构模型及其抑制剂的虚拟筛选(英文)

目的:构建SARS病毒类3C(3CL)蛋白酶的三维结构模型,根据这一模型设计3CL蛋白酶的抑制剂。方法:用生物信息学方法从GenBank和PDB库中搜寻出具有晶体结构并与SARS病毒3CL蛋白酶有较高同源型的蛋白质,以此为模板,用同源蛋白模建方法构建SARS病毒3CL蛋白酶的三维结构模型;针对模建的三维结构模型,进行高通量虚拟筛选,从现有小分子数据库中获得具有抑制SARS病毒3CL蛋白酶活性的化合物。结果:同源性分析表明SARS病毒3CL蛋白酶与遗传性肠胃炎主蛋白酶(TGEV M~(pro)),有较高的同源性,组成底物结合口袋残基的同源性更高。因此,可以根据TGEV M~(pro)的晶体结构为模板模建SARS病毒3CL蛋白酶的三维结构。 三维结构模型表明,ARS病毒3CL蛋白酶的结构与TGEV M~(pro)的结构非常相象,两个蛋白酶活性口袋的结构和形状儿乎一样。虚拟筛选测试研究表明,MRRD数据库中的73个蛋白酶抑制剂能与两个蛋白同时作用。结论:无论是SARS病毒3CL蛋白酶还是TGEV M~(pro)的晶体结构均可以作为设计抗SARS药物的结构模型。从现有的蛋白酶抑制剂中筛选抗SARS药物可能是一条好的途径。     

SARS传播的自回归模型

利用时间序列分析的方法 ,对北京市 2 0 0 3年 4～ 6月的 SARS疫情数据进行统计分析 ,分析表明用 AR(2 0 )模型来拟合传播过程的效果高度显著 ,并由此推定每个 SARS病人可以直接造成他人感染的期限平均在 2 0天左右。     

中国SARS疫情回顾分析

对中国 SARS疫情进行了回顾分析 ,得到非线性回归模型 N =2 0 5 -2 .11t1 .4 8,为今后预防 SARS疫情提供了比线性回归模型更为精确的决策依据     

新一代的杀菌消毒双链季铵盐化合物

<正> 目前非典型肺炎(SARS)在世界产生了巨大的影响,严重威胁人类健康和生命,世界各国都在各个领域研究如何抗击 SARS。WHO 称 SARS 综合症由一种来自冠状病毒科的病毒引起,SARS病毒感染的途径并不完全清楚,但在某些方面已经清楚。病毒可以从呼吸道分泌物、粪便及血液中发现,因此其传染途径可能有:通过空气、与传染者表面接触等。所以对皮肤及表面进行消毒是减少SARS 污染极为重要的措施。     

运用“五力模型”分析我国药品零售业的竞争力

＂五力模型＂的概念最早出现在著名的战略学大师迈克尔波特（Michael Porter）[1]1979年发表在《哈佛商业评论》题为《竞争力如何塑造战略》（How Competitive Forces Shape Strategy）的论文中。该论文的发表,历史性地改变了企业、组织乃至国家对战略的认识,被评为《哈佛商业评论》创刊以来最具影响力的十篇论文之一。     

基于Repast平台的SARS传播仿真建模研究

通过引入基于主体的建模思路和方法,根据易于描述的微观个体行为,利用Repast仿真建模平台对SARS的传播过程进行模拟,从而研究SARS传播宏观层面的规律,并根据謇验结果提出了疫情防控的策略和措施.本文初步构造了SARS传播的主体模型,定义了主体的状态转换方式以及主体之间的行为规则,并实现了一个可用于模拟SARS传播过程的简单的仿真建模框架,通过可动态扩展的规则设定、模型参数调节,为研究SARS传播提供了方便的模拟环境.     

SARS传播的Logistic模型及其推广

首先建立了 SARS传播的 Logistic模型 ,在此基础上建立了更符合实际的数学模型[1～ 4 ] ,能解释 SARS感染者被治愈后比未感染者有更强的免疫力等特点 ,并解析了模型的实际意义。     

真菌生物膜体内模型研究进展

生物膜是临床真菌感染的常见形式。以生物膜状态存在的真菌与浮游真菌存在很大不同。由生物膜引发的感染较难治愈。因此,开发对抗真菌生物膜的新手段成为了研究热点。动物体内模型可以更好地与宿主免疫系统联系起来,并且对于医疗器械相关生物膜感染的研究意义更加重大。本文选用白色念珠菌作为真菌研究对象。本文的主要目的就是介绍用于研究真菌生物膜的5种体内生物膜模型,并对这些模型的操作过程、应用、优势和不足进行介绍。     

大蒜中二烯丙基二硫化物对大鼠前列腺癌有化学预防作用

二烯丙基二硫化物(DADS)是蒜中的重要化合物,对人肿瘤如结肠癌、肺癌和皮肤癌有化学预防作用。ArmkuⅢar A发表论文称其采用体内模型,研究了DADS对SD大鼠前列腺癌的化学预防作用。     

国内引文数据库及其在大学评价中的作用

国内具有大学评价功能的引文数据库有CSTPC、CSCD、CSSC I和SCD。以上数据库收录的期刊可以被认为是具有机构学术水平评价功能的学术期刊,在这些期刊上发表论文可以提高论文作者所在院校论文发表数量这一指标,提高论文作者所在院校的科研绩效及其在国内的学术地位。     

Recent patents on treatment of severe acute respiratory syndrome (SARS)

Severe acute respiratory syndrome (SARS) is an epidemic that spread worldwide in early 2003. The aetiological agent was originally defined as a novel coronavirus and later designated as the SARS coronavirus (SARS-CoV), which appears similar to other coronaviruses in both virion structure and genome organization with a single-stranded, plus-sense RNA. However, the epidemiology and pathogenesis of SARS remain poorly understood and there is currently no effective treatment. To date, considerable research has been done on detection, prevention and treatment of SARS. In this review, we mainly focus on the recent patents and research work on detecting, preventing and treating SARS.     

Clinical management and infection control of SARS: Lessons learned

The outbreak of severe acute respiratory syndrome (SARS) in 2003 was the first emergence of an important human pathogen in the 21st century. Responding to the epidemic provided clinicians with extensive experience in diagnosing and treating a novel respiratory viral disease. In this article, we review the experience of the SARS epidemic, focusing on measures taken to identify and isolate patients, prevent the transmission of infection to healthcare workers and develop effective therapies. Lessons learned from the SARS epidemic will be especially important in responding to the current emergence of another highly pathogenic human coronavirus, the agent of Middle East respiratory syndrome (MERS), and to the recently emerging H7N9 influenza A virus in China. This paper forms part of a symposium in Antiviral Research on “From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.”     

Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics

At the time of writing this commentary (February 2020), the coronavirus COVID-19 epidemic has already resulted in more fatalities compared with the SARS and MERS coronavirus epidemics combined. Therapeutics that may assist to contain its rapid spread and reduce its high mortality rates are urgently needed. Developing vaccines against the SARS-CoV-2 virus may take many months. Moreover, vaccines based on viral-encoded peptides may not be effective against future coronavirus epidemics, as virus mutations could make them futile. Indeed, new Influenza virus strains emerge every year, requiring new immunizations. A tentative suggestion based on existing therapeutics, which would likely be resistant to new coronavirus mutations, is to use available angiotensin receptor 1 (AT1R) blockers, such as losartan, as therapeutics for reducing the aggressiveness and mortality from SARS-CoV-2 virus infections. This idea is based on observations that the angiotensin-converting enzyme 2 (ACE2) very likely serves as the binding site for SARS-CoV-2, the strain implicated in the current COVID-19 epidemic, similarly to strain SARS-CoV implicated in the 2002–2003 SARS epidemic. This commentary elaborates on the idea of considering AT1R blockers as tentative treatment for SARS-CoV-2 infections, and proposes a research direction based on datamining of clinical patient records for assessing its feasibility.     

SARS流行期高危医务人群与普通人群心理特点对比研究

目的 探讨SARS流行期间在岗高危医务人群及一般人群心理特点。方法 采用症状自评量表(SCL-90)、防御方式问卷(DSQ)和社会支持问卷(SSQ)，对SARS流行期间在岗的高危医务人群和一般人群的心理特征进行对比研究。结果 两群体SCL-90分数与常模比较，恐怖因子分一致上升和人际关系敏感因子分一致下降；高危人群组较一般人群组焦虑因子分升高，但高危人群组社会支持量表中对支持的利用度因子分高于一般人群组。结论 SARS流行期间疫区人群表现出独特的心理状态；高危医务人群虽然因承担更多的压力而表现出焦虑和躯体化，但该群体能较好地使用心理资源。     

Bioterrorism and emerging infectious disease - antimicrobials, therapeutics and immune-modulators. SARS coronavirus

The purpose of this meeting was to provide a forum for expert presentations and discussion about the threats of bioterrorism and emerging infectious diseases, and to address the issues relating to epidemics, prevention of infection and treatment of some of these emerging infectious diseases classified as potential agents of bioterror. Included in the talks were state-of-the-art presentations about infectious clone technology and recombinant viruses, pathogen and receptor interactions at the cellular and molecular level, genomic responses to infection, and new information on antiviral mechanisms of action. Severe acute respiratory syndrome (SARS) and progress toward understanding the epidemic was addressed, and other sessions were presented concerning immune therapy and immunopotentiation of disease, siRNA and gene silencing, host responses to pathogen infections, as well as the use of genetic engineering to circumvent and direct the immune response. Many discussions were held and data were presented about possible compounds and new drugs that may have antiviral properties, yet there were few discussions of any available new drugs. This report addresses reverse genetics of SARS virus, as well as its epidemiology, and a host of different recent approaches to developing antivirals effective against SARS, including some potential vaccine candidates. Also presented are hypotheses about the human immune response to SARS infection, as well as immune therapies against botulinum and anthrax toxins. This report also addresses antiviral approaches exploiting siRNAs, and different aspects of the host immune response to many of the different dangerous pathogens discussed at this meeting. Finally, approaches to circumventing and directing the immune response using genetic engineering will be reported.     

发热门诊与SARS传染病流行的关系

目的：探讨发热门诊在SARS传染病流行中的作用。方法：总结天津市SARS流行期间，我院发热门诊的患者组成及特点，采用归一化方法对比同期我市SARS病例的分布及2002年同期我院呼吸道感染急诊患者分布。结果：今年近一个月我院发热门诊累积就诊患者429例，转诊(定点医院)4例，其中确诊或疑似患者各1例。初诊病例以社区获得性呼吸道感染为主，占78．1％。2002年同期我院急诊呼吸道感染患者443例。今年同期天津市每日新增SARS确诊病例累计175例，其中医务人员67例。与去年同期相比，今年每日新增发热患者波动大，并呈现与SARS疑似患者相似的消长趋势，与SARS确诊患者峰值出现时间亦相近。结论：SARS流行期间我院发热门诊以普通发热病人为主，SARS患者不多，这与本市SARS流行期间，SARS病例以医院感染为主的特点相一致。急性发热患者数波动高峰是否有轻型SARS感染患者的参与尚待日后进一步研究。     

抗生素在严重急性呼吸综合征诊断中作用的探讨

目的探讨抗生素在严重急性呼吸综合征(SARS)诊断中的作用。方法对太原市定点医院的304例住院确诊SARS病例住院前临床症状及抗生素的使用情况进行分析、评价。结果304例SARS患者主要的临床症状有发热298例,占98.0%;咳嗽161例,占53.0%;乏力156例,占51.3%;全身肌肉酸痛95例,占31.3%;咯痰84例,占27.6%;畏寒85例,占27.3%;少数有头痛、咽痛、关节痛、呼吸困难、恶心呕吐、腹痛及腹泻等。77%的SARS患者在入院前使用了抗生素,其中98%治疗效果为无效、差或一般。123例有明确的流行病学接触史,占40.5%。早期白细胞正常或下降的SARS患者有213例,占93.4%。结论SARS患者临床症状以全身症状(如发热、寒战、乏力、肌痛及畏寒)和呼吸道症状(如咳嗽、气促及呼吸困难)为主;多数有明确的流行病学接触史及抗生素治疗史,而且抗生素治疗无效为特征。     

我国新型冠状病毒疫苗研发进展及思考

新型冠状病毒(SARS-CoV-2)是继SARS冠状病毒(SARS-CoV)和中东呼吸综合征冠状病毒(MERS-CoV)之后又一严重危害人类的病毒。SARS-CoV-2引起的疾病被世界卫生组织命名为COVID-19,具有较高的传染性和病死率。为控制疫情蔓延,我国正应急开展多种技术路线的COVID-19疫苗研发,包括灭活疫苗、重组蛋白疫苗、病毒载体疫苗和核酸疫苗(DNA和mRNA)等,在加快疫苗研发进程的同时把握应急研发进度和科学性之间的平衡,并行解决相关科学问题,在满足安全性的前提下保证疫苗的有效性和质量可控。目前我国研发的腺病毒载体疫苗已率先进入Ⅰ期临床试验,多家企业进入注册检验和滚动提交审评资料阶段。本文对COVID-19疫苗研究进展进行综述,并提出现阶段对此种新疫苗研发的考虑。     

SARS期间抗菌药物应用分析

目的:了解SARS期间抗菌药物应用情况,为临床合理使用抗菌药物以及寻找更佳治疗方案提供参考。方法:对两家医院SARS病人使用抗菌药物情况按销售金额和DDDs值进行统计分析。结果:所使用的抗菌药物种类全、用量较大且起点高,易产生耐药现象及二重感染。结论:应控制抗菌药物使用。开发新一代抗菌药物和抗SARS特效药是当前的重要任务。