Identification of Host Cellular Protein Substrates of SARS-COV-2 Main Protease

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-19 (COVID-19) being associated with severe pneumonia. Like with other viruses, the interaction of SARS-CoV-2 with host cell proteins is necessary for successful replication, and cleavage of cellular targets by the viral protease also may contribute to the pathogenesis, but knowledge about the human proteins that are processed by the main protease (3CLpro) of SARS-CoV-2 is still limited. We tested the prediction potentials of two different in silico methods for the identification of SARS-CoV-2 3CLpro cleavage sites in human proteins. Short stretches of homologous host-pathogen protein sequences (SSHHPS) that are present in SARS-CoV-2 polyprotein and human proteins were identified using BLAST analysis, and the NetCorona 1.0 webserver was used to successfully predict cleavage sites, although this method was primarily developed for SARS-CoV. Human C-terminal-binding protein 1 (CTBP1) was found to be cleaved in vitro by SARS-CoV-2 3CLpro, the existence of the cleavage site was proved experimentally by using a His₆-MBP-mEYFP recombinant substrate containing the predicted target sequence. Our results highlight both potentials and limitations of the tested algorithms. The identification of candidate host substrates of 3CLpro may help better develop an understanding of the molecular mechanisms behind the replication and pathogenesis of SARS-CoV-2.     

SARS流行预测分析

表面上突如其来的SARS本质上却有极规律的内在发展演化机制，遵从初始缓慢增长、加速、减速和稳定终止四个阶段总体道路，自然和社会生活领域众多事件演化都符合这一规律，因而可以运用广义的Logistic生长模型进行描述。基于先期流行的广东SARS感染病例数据，以及尚未结束的北京、全国2003年SARS流行统计数据，借助于最优化分析技术，运用广义的Logistic生长模型对该事件演化特征参量进行了辨识；在此基础上，又借助于广义生长模型的特例——Gompertz函数进行了演化过程的预测，并与其他生长模型结果进行了比较。研究表明，生长模型模拟结果均与实际数据有很好的一致性，可以用来预测事件的发生演化过程，此次SARS事件堪称生长模型的经典实例。     

抗非典药皮质激素的关键中间体甾醇项目可行性探讨

谷甾醇是抗非典药糖皮质激素的关键中间体,其市场需求量将显著增长。中国的竞争策略宜自主开发具有国际竞争力的核心技术,含对米糠原料的开发与控制;全球约37%的米糠产于中国,米糠油是含不皂化物最多的植物油脂(3.5%～5.2%),不皂化物中70%以上为甾醇,中国是甾醇原料大国。以米糠为原料,在水稻化工厂"4联产"或"9联产"等多联产技术系统中生产谷甾醇,其利润空间较大。     

SARS灭活疫苗的研制及其质量控制

目的研究适合SARS病毒灭活疫苗的生产工艺及其质量控制。方法连续制备3批疫苗,按拟定规程进行疫苗原液和疫苗各项指标检测。结果各项检测指标均符合拟定规程规定。结论我所生产的SARS灭活疫苗工艺稳定,质量可控。     

SARS风暴·从众心理·传媒责任

SARS风暴给生命健康带来严重威胁,但最大的影响是从众心理诱发的巨大恐慌.高度专制的封建社会是从众心理的历史根源;异常稳固的自然经济是从众心理的经济土壤;儒家独尊的文化格局是从众心理的思想温床;中国人的自身特点是从众心理的内质载体."科教兴国"战略是消除从众心理负面影响的有效途径,传媒对正确引导社会舆论有着不可推卸的责任.     

用人工神经网络对SARS疫情进行分析与预测

采用三层结构的反向传播网络(backpropagationnetwork,简称BP网络),对SARS在中国的传播与流行趋势及控制策略建立了网络模型.并利用实际数据拟合参数,针对山西的疫情进行了计算仿真.结果表明,该网络模型算法收敛速度较快,预测精度很高.     

Imperative role of electron microscopy in toxicity assessment: A review

Electron microscope (EM) was developed in 1931 and since then microscopical examination of both the biological and non-biological samples has been revolutionized. Modifications in electron microscopy techniques, such as scanning EM and transmission EM, have widened their applicability in the various sectors such as understanding of drug toxicity, development of mechanism, criminal site investigation, and characterization of the nano-molecule. The present review summarizes its role in important aspects such as toxicity assessment and disease diagnosis in special reference to SARS-COV2. In the biological system, EM studies have elucidated the impact of toxicants at the ultra-structural level in various tissue in conformity to physiological alterations. Thus, EM can be concluded as an important tool in toxicity assessment and disease prognosis.     

Predictive factors of psychological disorder development during recovery following SARS outbreak.

Objective: To investigate strategies for broad mass isolation during outbreaks of infectious diseases. Design: A survey using a self-administered questionnaire was conducted on 300 printing company workers in Beijing, China, which was under mass isolation following the 2003 SARS outbreak, in the 7-8 months after the isolation was lifted. Main Outcome Measures: Individuals with psychological disorders were classified on the basis of scores on the 30-item General Health Questionnaire during the recovery period. Psychological disorders were observed in 49 of 187 respondents (26.2%; 95% CI = 20.2, 32.7). Results: The predicting factor with the highest correlation was income reduction, with an odds ratio of 25.0. Other items obtained were gender, range of activities, eating restrictions, restrictions in going out, disinfection of clothing, and infection control, with odds ratios of 3.2, 5.5, 3.9, 3.2, 0.2, and 0.1, respectively, and the contribution ratio was 87.7%. Conclusion: Securing income is suggested to be important in future strategies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

考虑自愈的SARS的传播模型

本文根据对SARS传播的分析,把人群分为5类:易感类、潜伏期类、患病未被发现类、患病已被发现类和治愈及死亡组成的免疫类,并考虑自愈因素,提出了两个模型:微分方程模型和基于SmallWorld Network的模拟模型.对微分方程模型,以香港为例讨论了自愈的影响,在一定意义下说明自愈现象在SARS传播中是普遍存在的.模拟模型利用Small-World Network[1]模拟现实中人们之间的接触;借鉴Sznajd模型[2]观念传播的基本思想"考察区域内每个成员如何影响与其有联系的其他成员",用影响类比传染,从患病者去传染与其有接触的健康人的角度,模拟SARS的传播过程;然后吸收元胞自动机模型[3]同步更新的思想,最终建立了一个患病者传染邻居,且一个成员同时受所有邻居影响的基于Small-WorldNetwork的模拟模型.对此模型,我们讨论了一些主要参数及接种疫苗的影响,最后拟合北京数据,讨论了提前或推迟5天采取措施的影响.     

Mechanistic Study of the Reaction of Thiol‐Containing Enzymes with α,β‐Unsaturated Carbonyl Substrates by Computation and Chemoassays

We investigated the reactions between substituted α,β‐unsaturated carbonyl compounds (Michael systems) and thiols by computations as well as chemoassays. The results give insight into variations in the underlying mechanisms as a function of the substitution pattern. This is of interest for the mechanisms of inhibition of the SARS coronavirus main protease (SARS‐CoV M^pro) by etacrynic acid derivatives as well as for the excess toxicity of substituted α,β‐unsaturated carbonyl compounds. This study compares possible reaction courses including 1,4‐addition followed by a ketonization step, and underscores the importance of a base‐catalyzed step for the reactivity of thiol groups in enzymes. Phenyl and methyl substituents at the Michael system decrease the reactivity of the electrophilic compound, but chlorophenyl substituents partly recover the reactivity. Computations also indicate that electron‐pushing substituents lead to a change in the reaction mechanism. The conformation of the Michael system is also found to significantly influence reactivity: the s‐cis conformation leads to higher reactivity than the s‐trans conformation. The computed data explain the trends in measured inhibition potencies of substituted α,β‐unsaturated carbonyl compounds and of reaction rates in chemical assays. They also indicate that the reversibility of inhibition does not stand in contrast to the formation of a new covalent bond between inhibitor and protease.