Huu S. TIEU’s Predicting Outcome of Severe Acute Respiratory Syndrome (SARS) and Preparing the Treatment for COVID-19 (Coronavirus) and Other Viral Pandemics

This project paper is to give a prediction for the future of other viral pandemics and to provide recommendations for preparing therapies that could help in the success of effective treatments and benefits for patients in life-threatening situations. The theory of prediction was proposed by Huu S. TIEU on March 25, 2019, and he hypothesized that any malfunctioning cell in the body could have a damaging effect. This paper discusses the prediction that Localized Oxygen Deprivation could be a contributing factor for a future epidemic or other viral pandemics that could affect body function. This paper is based on opinion and does not have sufficient evidence to support the claims made. Therefore, further in-depth study is needed to prove the findings. The author cites Hypoxia to support his idea, but he is not claiming that Hypoxia-Inducible Factor (HIF) has worked on his predictions. The author also tested a theory using cow blood curd for body function, but this test was not a structured test and the findings were not supported by other evidence. To further prove the idea or theory, further study into the subject should be conducted.

Elevated Plasma Tissue-type Plasminogen Activator (t-PA) and Soluble Throm-bomodulin in Patients Suffering From Severe Acute Respiratory Syndrome (SARS) as a Possible Index for Prognosis and Treatment Strategy

To detect the presence of endothelial injury in patients with severe acute respiratory syndrome （SARS） via enhanced levels of tissue-type plasminogen activator （t-PA） and soluble thrombomodulin （sTM）. Methods Case patients were from Xuanwu Hospital （Capital University of Medical Sciences, Beijing, China）, and all of them met clinical criteria for SARS. Healthy controls were some of the hospital employees. Endothelial injury bio-markers tPA and sTM were detected by commercial ELISA-methods. Results Classic plasma markers of endothelial injury, tPA and sTM significantly elevated in SARS patients in comparison to controls [t-PA： 1.48±0.16 nmol/L versus 0.25±0.03 nmol/L （P〈0.0001）, and sTM： 0.26±0.06 nmol/L versus 0.14±0.02 nmol/L （P〈0.05）]. The only patient who died had extremely high levels of these endothelial injury markers （t-PA： 2.77 nmol/L and sTM： 1.01 nmol/L）. The likelihood ratio analysis indicated the excellent discriminating power for SARS at the optimal cut-point of 0.49 nmol/L for tPA and 0.20 nmol/L for sTM, respectively. Significant numerical correlations were found among these endothelial injury markers in SARS patients. The numerical coefficient of correlation Pearson r between t-PA and sTM was 0.5867 （P〈0.05）. Conclusion Increased plasma concentrations of tPA and sTM in patients with SARS suggest the possibility of endothelial injury. SARS patients might need anticoagulant therapy or fibrinolytic therapy in order to reverse intraalveolar coagulation, microthrombi formation, alveolar and interstitial fibrin deposition. It may not only provide a useful treatment and prognostic index but also allow a further understanding of the pathological condition of the disease.

A Case of Severe Acute Respiratory Syndrome (SARS) Coronavirus 2 in Pregnancy: A Multidisciplinary Approach

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) is a truly novel, multifaceted disease that has negatively impacted the lives of many including the pregnant women. We present a 34-year-old pregnant patient at 35 weeks with SARS-COV-2 requiring emergent cesarean section under general endotracheal anesthesia and a prolonged postoperative course in the ICU with multiple end organ function derangement of this disease. After nearly 1 month, she was discharged home. Her baby did not have any manifestations of SARS-COV-2 and was able to go home after 5 days.

The role of immunoinformatics in analysis of immune response against severe acute respiratory syndrome (SARS) coronavirus

In order to analyze the immune response to severe acute respiratory syndrome （SARS） coronavirus （SARS-CoV）, immunoinformatics and computational analyses were performed to study the immunological characters of SARS-CoV. According to the results of immunoinformatics analysis, the obvious variation of HLA-A2 associated T cell epitopes between SARS vires and HCoV-229E was found as follows： （1） Disappearance of HIA-A2 binding site; （2） variation sequence on the HLA-A2 associated epitope; （3） emergence of a new HLA-A2 associated epitope. The immunoinfomatics results were evidenced by T2 cell binding assay, ELISPOT and DimerX staining. In conclusion, immunoinformatics is a useful method to analyze the immunological character of a new finding infectious pathogen, like SARS-CoV. These findings of immunoinformatics are confirmed by lab and clinical experiments. In this case, immunoinformatics seems a very useful tool in the study of immune response and the evaluation of vaccine in infectious diseases, such as SARS.

Epidemiological Characteristics of An Outbreak of Severe Acute Respiratory Syndrome in Dongcheng District of Beijing From March to May 2003

Objective To describe epidemiologic features of an outbreak of severe acute respiratory syndrome (SARS) in Dongcheng District, Beijing occurred in a period between March and May 2003. Methods Data of SARS cases notified from Dongcheng District Center for Disease Control and Prevention (CDC )and supplemented by other channels were collected. Clinicians and officials of local hospitals were interviewed in groups and medical records of fatal cases of SARS were reviewed to verify the diagnosis. Stored serum specimens of the patients were detected for IgG antibody against SARS Co-V by enzyme-linked immunosorbent assay (ELISA). All the data were input into dataset files by Microsoft Excel-2000 software and analyzed with SPSS version 10.0 software. Results Outbreak of SARS in Dongcheng District started on March 14, 2003 with a peak in mid- and late April, and dropped in early May. A total of 572 reported cases were collected during this period in Dongcheng District, Beijing, and 99 of them were excluded from SARS, because of diagnosis of common cold, regular pneumonia, measles and rubella, etc. Actually, 473 SARS cases, which included 390 (82.5%) probable cases and 83 (17.5%) suspect cases, were analyzed. About 90% of the probable cases were positive for IgG antibody. Attack rate of SARS in permanent residents of Dongcheng District was 28.3 per 100 000. Forty-one of them died, with a case-fatality rate of 8.7%. Persons were all susceptible to infection of SARS Co-V, with the highest proportion at ages of 20-50 years, which accounted for 68.7% of the total cases. Average age of the patients at their onset was 40.7 years. No gender difference in SARS cases was found. Number of SARS cases in health-care workers (HCWs) accounted for 18.0% and that in retired workers accounted for 15.4% of the total cases. Cases occurred in all 10 sub-districts of Dongcheng, with the highest in Beixinqiao and Andingmen Sub-districts. Totally, 230 of the 572 notified cases (40.2%) were hospitalized at local hospitals under the jurisdiction of Dongcheng District. Eighteen of 85 cases of SARS occurred in HCWs of local hospitals, accounting for 4.5% of the total number of HCWs working at wards caring for SARS patients or fever clinics. There were 34.7% of SARS cases without any histories of contact before the onset of the disease. Familial aggregation phenomena were observed in 41.8% of the cases and 18.1% of households. And 7.4% (attack rate ) of those exposed to SARS cases suffered from the illness during the periods of quarantine. Conclusions SARS appeared to be infectious in origin and caused outbreak in Dongcheng District, Beijing introduced by an imported case traveling from Hong Kong in a period between March and May 2003. People are all susceptible to infection of SARS Co-V, which mainly threatens the young adults and the middle-aged, as well as HCWs and the retired workers. The main mode of transmission is direct exposure to SARS patients in a near distance at hospitals or families via droplets spread. Prevention and control of SARS should be focused on early isolation of patients and quarantine for close contacts. Current available measures to prevent and control SARS are proved to be effective.

Analysis and Comparison of the Tongue Picture of 34 Patients with Severe Acute Respiratory Syndrome

Objective: To explore the changes of tongue pictures in the developing process of disease in patients with severe acute respiratory syndrome (SARS), and to compare the tongue pictures of SARS patients with those of suspected SARS patients. Methods: Materials of tongue picture were dynamically collected from 34 SARS patients and 35 suspected SARS patients, and the difference and similarity between them were analyzed. Meanwhile, the changes in clinic symptoms and tongue picture after integrative medicinal treatment were observed. Results: Characteristics of tongue picture in SARS patients were changed along with the progress of the disease, showing that there existed a tendency of the pathogen invading from exterior to interior, from surface to the deep. Also the tongue pictures were varied due to the coexistence of dampness pathogen; the time of the early stage was generally 1 - 1.5 days, shorter than that of other stages. While in the patients with suspected SARS, the tongue picture was mostly red with thin white or yellow coating, comparatively steady and showing no obvious change along with the development of the disease. Conclusion: Observing the tongue picture and its changes in different stages can be helpful to understanding the property of pathogenic evil and its developing rules, thus offering a basis for clinical treatment.

Severe Acute Respiratory Syndrome-Retrospect and Lessons of 2004 Outbreak in China

Objective To summarize lessons learned from an outbreak of severe acute respiratory syndrome （SARS） in China during the spring of 2004. Methods Data of SARS cases were officially reported by Beijing Municipal Center for Disease Control and Prevention （BCDC） and Anhui Provincial Center for Disease Control and Prevention （APCDC） and results of epidemiological investigations were collected and analyzed. Results Three generations of 11 cases of SARS were identified during the outbreak, Initial two cases were most likely to be infected in Diarrhea Virus Laboratory of National Institute of Virology, China Centers for Disease Control and Prevention and main mode of transmission was direct contact with SARS patients, Delay in detecting initial case resulted in spread of the illness at hospitals and communities with two generations of secondary cases, Conclusions SARS outbreak in 2004 has yielded following lessons for public health globally. （1） Lab bio-safety programs should be made and should be strictly abided by, Studies in highly pathogenic viruses such as SARS coronavirus should be utmost cautious, （2） Management systems of occupational exposure to virus and disease surveillance need to be strengthened to take all risk factors into account so as to detect potential patients with infectious disease as early as possible.

Expression of Prothrombinase/fibroleukin Gene fg12 in Lung Impairment in a Murine Severe Acute Respiratory Syndrome Model

To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.

Clinical and Spatial Characteristics of Severe Acute Respiratory Syndrome by COVID-19 in Indigenous of Brazil

The new coronavirus (SARS-CoV-2) broke out in Wuhan in China in December 2019, causing severe pneumonia and deaths, soon in March 2020, it reached pandemic level, affecting several countries including Brazil. The disease was named COVID-19, with characteristics of most infected having mild and moderate symptoms and a part severe symptom. The disease has already reached 158 ethnic groups, which have high vulnerability and limited access to health services. The objective is to investigate the clinical and spatial characteristics of Severe Acute Respiratory Syndrome of COVID-19 in the indigenous peoples of Brazil. It is an epidemiological, cross-sectional, analytical ecological study, based on data from the OpenDataSUS platform from 01/01/2020 to 31/08/2020. Profile variables, signs and symptoms and risk factors/comorbidities. The data were analyzed by Bioestat 5.3. There were 1,207 cases and 470 deaths. Profile: male gender (59.48%) means age 53 years. Signs and symptoms: fever (74.23%), cough (77.71%), sore throat (35.62%), dyspnea (69.34%), respiratory discomfort (62.80%), O2 saturation < 95% (56.42%);and associated with mortality: dyspnea (80.0%) and O2 saturation < 95% (69.36%). Risk factors and comorbidities (45.89%) were associated with deaths (54.04%). About comorbidities, chronic cardiovascular diseases represented (18.97%) and Diabetes Mellitus (18.97%), and associated with deaths: Chronic Cardiovascular Disease (24.46%). Being admitted to the ICU has a risk of death in (OR-3.96- < 0.0001-CI-2913/5383) followed by not being vaccinated against influenza (OR-1.85- < 0.0001-CI-1358/2528). The public and health policies of Brazil should be directed to control the dissemination of COVID-19 in this population, that COVID-19 evolves in the same intensity, however, the indigenous have vulnerabilities that can increase the impact of the pandemic in this population.

SARS-COV-2 M^(pro)抑制剂2-(2-氯苯基)-7-(异喹啉-4-基)-5,7-二氮杂螺[3.4]辛-6,8-二酮的合成

目的研究SARS-COV-2 M^(pro)抑制剂2-(2-氯苯基)-7-(异喹啉-4-基)-5,7-二氮杂螺[3.4]辛-6,8-二酮(1)的合成方法,为其深入研究和其衍生物的合成提供借鉴方法。方法以(2-氯苯基)乙酸甲酯为起始原料,经亲电取代、还原、磺酰化、环化、选择性水解得到3-(2-氯苯基)-1-乙氧羰基环丁烷-1-甲酸(6),在三乙胺存在下,化合物6与叠氮磷酸二苯酯反应,生成的酰基叠氮化合物经Curtius重排生成相应的异氰酸酯;再与4-氨基异喹啉反应,并在碳酸钠的作用下进一步环合生成目标化合物。结果中间体及目标化合物的化学结构经^(1)H-NMR、^(13)C-NMR、ESI-MS确证。结论对化合物6的合成路线进行了优化;通过化合物6获得了一条更精简的化合物1的合成路线,该路线既避免了有毒的三光气的使用,也避免了副反应的发生;通过制备型HPLC得到化合物1的两个顺反异构体,并使用NOESY确定了化合物的构型。

SARS-CoV-2靶向CypA/CD147受体途径诱导心肌细胞凋亡

目的探究SARS-CoV-2靶向亲环素A(CypA)/细胞外金属蛋白酶诱导剂(CD147)受体途径诱导心肌细胞凋亡的可能机制。方法构建pEncmv-SARS-CoV-2 S-3xflag重组载体质粒转染H9c2细胞,TUNEL实验、流式细胞术和DNA ladder分析细胞凋亡,免疫共沉淀(CoIP)验证CD147与SARS-CoV-2 S蛋白之间相互作用,Western blotting法检测细胞凋亡信号通路相关蛋白表达。结果与对照组比较,TUNEL实验和流式细胞术结果显示转染组细胞凋亡显著增加(P<0.05),DNA ladder分析发现DNA降解明显。Western blotting法检测显示Caspase12、DR3表达显著升高(P<0.001),FAS表达升高(P<0.01),TRF1、DR4表达降低(P<0.01)。结论SARS-CoV-2 S蛋白靶向CypA/CD147受体入侵宿主细胞,激活内质网通路(Caspase12)和死亡受体通路(DR3、FAS),以内源性和外源性凋亡途径诱导心肌细胞凋亡。

熊去氧胆酸对小鼠ACE2受体的影响及感染SARS-CoV2-的效果

在新型冠状病毒(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染过程中,验证使用熊去氧胆酸(ursodeoxycholic acid,UDCA)在BALB/c小鼠体内是否具有降低血管紧张素转化酶2(angiotensin-converting enzyme 2,ACE2)受体的作用及降低感染风险。UDCA通过灌胃给药方式连续治疗BALB/c小鼠7 d,治疗过程中每天取小鼠鼻甲骨和肺脏,并通过ELISA检测小鼠鼻甲骨和肺脏中ACE2含量的变化;另外使用UDCA对BALB/c小鼠进行灌胃预防1、4、7 d后,分别滴鼻感染SARS-CoV-2 C57MA14鼠适应株和SARS-CoV-2 Omicron DY1.1,攻毒后3 d取小鼠鼻甲骨和肺脏检测病毒载量评价预防效果;此外使用UDCA对滴鼻感染SARS-CoV-2 C57MA14鼠适应株后的BALB/c小鼠进行灌胃治疗3 d,取小鼠鼻甲骨和肺脏检测病毒载量评价治疗效果。UDCA可以降低BALB/c小鼠鼻甲骨和肺脏中ACE2的含量;用UDCA灌胃1、4、7 d后的预防组和病毒对照组的BALB/c小鼠的鼻甲骨和肺脏中的病毒载量无统计学差异;UDCA治疗组与病毒对照组的鼻甲骨和肺脏的病毒载量之间无统计学差异。UDCA可以降低老龄BALB/c小鼠鼻甲骨和肺脏中ACE2的含量,但用UDCA治疗的每日剂量和持续时间对小鼠感染SARS-CoV-2 C57MA14鼠适应株和SARS-CoV-2 Omicron DY1.1无明显影响。

Symptomatic COVID-19 in University Students: A School-Wide Web-Based Questionnaire Survey during the Omicron Variant Outbreak

Aim: To detect risk and preventive factors associated with the Omicron variant infection in university students, a combination of a web-based survey and multivariate logistic regression analysis was introduced as the front-line initiatives by the school health practitioners. Design: Questionnaire survey. Methods: The school-wide web-based questionnaire survey was conducted among our university students as a part of the annual health check-up in April, 2023. The positive outcome was confined to the first symptomatic COVID-19 onset during the Omicron variant outbreak. Results: In this self-administered survey, risk or protective associations were merely estimated statistically in university students (n = 5406). In measured factors, karaoke and club/group activities could maintain the statistical significance in adjusted odds ratios (ORs) as relative risk factors, and science course, measles/ rubella (MR) vaccination, and COVID-19 vaccination remained as relative protective factors in adjusted OR analyses. Club/group activities with member gathering and karaoke sing-along sessions in university students may frequently have WHO’s three Cs. These risk factors are still important topics for the infection control of COVID-19 in university students. Together with some recent reports from other researchers, the significant protective role of MR vaccine in our survey warrants further clinical investigation. If the breakthrough infection continuously constitutes the majority of infection, real data in test-negative case-control or web-based questionnaire design continue to be important for statistical analysis to determine the minimal requirement of our strategies which may be equivalent to or replace COVID-19 vaccines.

The difference of immunologic parameters between SARS patients of mild type and severe type

The aim of this study is to study the difference of immunologic parameters between severe acute respiratory syndrome （SARS） patients of mild type and severe type. Data including white blood cell （WBC） count, lymphocyte count, CD3, CD4 and CD8 T lymphocyte count, levels of C3, C4, ESR （erythrocyte sedimentation rate） and CRP （C-reactive protein） from 1291 patients with SARS in each week from onset of illness were recorded. The clinical progress of each sign was analysed and the difference between mild type and severe type was compared. Lymphocyte count, CD8 T lymphocyte count declined in the first two weeks and recovered from the third week, while CRP and CA- levels rose in the first week and then recovered gradually. Lymphocyte count and CD8 T lymphocyte count of severe cases were much lower than that of mild type （P 〈 0.01）, while CRP and CA- levels in severe type were much higher than that of mild type （P 〈 0.01）. Lymphocyte count, CD8 T lymphocyte count, CRP and CA- levels are useful signs for the diagnosis of SARS of severe type and are valuable for the evaluation of its severity.

Site discrepancy of synonymous codon usage in SARS coronavirus and other viruses in Coronaviridae

The synonymous codon usage in the translational initiation and termination regions of genes of severe acute respiratory syndrome (SARS) coronavirus and five other viruses in Coronaviridae was systematically analyzed.The results indicate that most minor codons for these coronaviruses are preferentially used in the initial and terminal region.The minor codons preferentially used in the initial region are thought to have a negative effect on gene expression,which can be explained by the minor codon modulator hypothesis.It also indicates that the minor codons preferentially used in the terminal region may regulate the level of gene expression.The proposed results strongly imply that the minor codon modulator hypothesis can be applied to both some bacteria and some viruses.

Katalin Karikó和Drew Weissman助力研发抗新型冠状病毒mRNA疫苗荣获2023年诺贝尔生理学或医学奖

北京时间2023年10月2日瑞典斯德哥尔摩卡罗琳学院宣布,将诺贝尔生理学或医学奖授予美国匈牙利裔科学家卡塔琳·卡里科(Katalin Karikó)和美国科学家德鲁·魏斯曼(Drew Weissman),以表彰他们在核苷碱基修饰方面的发现,进而为研发有效的抗新型冠状病毒(severe acute respiratory syndrome coronavirus 2,SARS CoV-2)疫苗做出了杰出贡献。本文将介绍两位科学家的简历、主要科学贡献和他们科学发现的意义。

基于分子对接和分子动力学模拟技术筛选SARS-CoV-23CL蛋白酶抑制剂

目的 以分子对接和分子动力学模拟技术相结合的方法筛选得到严重急性呼吸系统综合征冠状病毒2 (severe acute respiratory syndrome coronavirus 2,SARS-CoV-2) 3CL蛋白酶的小分子抑制剂。方法 基于SARS-CoV-2 3CL蛋白酶的晶体结构(PDB ID:7K3T和7SI9),从PubChem数据库中筛选得到SARS-CoV-2 3CL蛋白酶的特异性抑制剂nirmatrelvir的结构类似物,使用Autodock进行非共价分子对接,使用AutoDockFR进行共价分子对接,采用Pymol和Ligplot软件对SARS-CoV-2 3CL蛋白酶和小分子进行相互作用模式分析,最后使用AMBER18进行小分子化合物与SARS-CoV-2 3CL蛋白酶复合物的分子动力学模拟,进一步验证分子对接结果,使用SwissADME对化合物进行成药性分析。结果 将78个nirmatrelvir结构类似物与SARS-CoV-2 3CL蛋白酶进行虚拟筛选和分子对接,得到了2个与nirmatrelvir作用相当的小分子化合物(PubChem ID:57842182和156619968),共价对接发现化合物57842182和化合物156619968与SARS-CoV-2 3CL蛋白酶间不存在共价结合。分子动力学模拟结果表明化合物57842182、化合物156619968与SARS-CoV-2 3CL蛋白酶的结合自由能(ΔE_(total))分别为-23.96 kcal·mol^(-1)和-27.11 kcal·mol^(-1),二者主要通过与MET165、GLU166、ASN142、CYS145、LEU50、MET49等氨基酸残基的相互作用占据SARS-CoV-2 3CL蛋白酶亚活性位点,具有潜在抑制SARS-CoV-2 3CL蛋白酶活性的功能。化合物57842182和化合物156619968的成药性略差于nirmatrelvir。结论 筛选得到的nirmatrelvir结构类似物57842182和156619968具有作为新型冠状病毒SARS-CoV-2 3CL蛋白酶小分子抑制剂的潜力,其与SARS-CoV-2 3CL蛋白酶的结合特点可为SARS-CoV-2 3CL蛋白酶抑制剂的药物设计提供线索。

Molecular Advances in Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV)

The sudden outbreak of severe acute respiratory syndrome (SARS) in 2002 prompted the establishment of a global scientific network subsuming most of the traditional rivalries in the competitive field of virology. Within months of the SARS outbreak, collaborative work revealed the identity of the disastrous pathogen as SARS-associated coronavirus (SARS-CoV). However, although the rapid identifi-

中医药治疗SARS疗效Meta分析及对新冠肺炎防治的启示

目的目前新冠肺炎疫情肆虐全球,与SARS同属冠状病毒感染。系统评价中医药治疗SARS的疗效,为新冠治疗提供参考。方法检索中医药治疗SARS的随机对照试验,由两名评价者对检索文献进行分析,将符合标准的文献纳入本次系统评价范畴,并进行Meta分析。结果16个研究符合纳入标准,系统研究中共纳入患者1574例,其中试验组820例,对照组754例。16项研究中有效率的研究,通过异质性检验,χ^(2)=12.22,df=14,P=0.59,I2=0%,采用固定效应模型,OR=5.23(95%CI=3.38~8.08),Z=7.45,P<0.01,提示中医药治疗SARS有效率高,且有统计学意义。结论中医药治疗SARS疗效显著,明显优于西医疗法,对新冠肺炎的防治有参考意义。