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A comparative analysis of epidemiological characteristics of mers-cov and SARS-cov-2 in Saudi Arabia

Infectious Disease Modelling 2022年第3期7卷 473-485页

作者： Yehya Althobaity Jianhong Wu Michael J.Tildesley The Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research School of Life Sciences and Mathematics InstituteUniversity of WarwickCoventryCV47ALUnited Kingdom Laboratory for Industrial and Applied Mathematics Department of Mathematics and StatisticsYork UniversityTorontoOntarioM3J 1P3Canada Department of Mathematics Taif UniversityTaifP.O.Box 11099Saudi Arabia

In this study,we determine and compare the incubation duration,serial interval,pre-symptomatic transmission,and case fatality rate of mers-cov and covID-19 in Saudi Arabia based on contact tracing data we acquired in Saudi *** date of infection and infector-infectee pairings are deduced from travel history to Saudi Arabia or exposure to confirmed *** incubation times and serial intervals are estimated using parametric models accounting for exposure interval *** estimations show that mers-cov has a mean incubation time of 7.21(95%CI:6.59–7.85)days,whereas covID-19(for the circulating strain in the study period)has a mean incubation period of 5.43(95%CI:4.81–6.11)***-cov has an estimated serial interval of 14.13(95%CI:13.9–14.7)days,while covID-19 has an estimated serial interval of 5.1(95%CI:5.0–5.5)*** covID-19 serial interval is found to be shorter than the incubation time,indicating that pre-symptomatic transmission may occur in a significant fraction of transmission *** conclude that during the covID-19 wave studied,at least 75%of transmission happened prior to the onset of *** CFR for mers-cov is estimated to be 38.1%(95%CI:36.8–39.5),while the CFR for covID-191.67%(95%CI:1.63–1.71).This work is expected to help design future surveillance and intervention program targeted at specific respiratory virus outbreaks,and have implications for contingency planning for future coronavirus outbreaks.

关键词： mers-cov SARS-cov-2 Incubation period Serial interval Pre-symptomatic transmission Case fatality rate

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Molecular Characteristics,Functions,and Related Pathogenicity of mers-cov Proteins

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Engineering 2019年第5期5卷 940-947页

作者： Yan-Hua Li Chen-Yu Hu Nan-Ping Wu Hang-Ping Yao Lan-Juan Li State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Hangzhou 310003China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 31003China

Middle East respiratory syndrome(mers)is a viral respiratory disease caused by a de novo coronavirus—mers-cov—that is associated with high ***,the mechanism by which mers-cov infects humans remains *** date,there is no effective vaccine or antibody for human immunity and treatment,other than the safety and tolerability of the fully human polyclonal Immunoglobulin G(IgG)antibody(SAB-301)as a putative therapeutic agent specific for *** rapid diagnostic and public health measures are currently being implemented,new cases of mers-cov infection are still being ***,various effective measures should be taken to prevent the serious impact of similar epidemics in the *** investigation of the epidemiology and pathogenesis of the virus,as well as the development of effective therapeutic and prophylactic anti-mers-cov infections,is *** this purpose,detailed information on mers-cov proteins is *** this review,we describe the major structural and nonstructural proteins of mers-cov and summarize different potential strategies for limiting the outbreak of *** combination of computational biology and virology can accelerate the advanced design and development of effective peptide therapeutics against *** summary,this review provides important information about the progress of the elimination of mers,from prevention to treatment.

关键词： mers-cov Spike protein Structural protein Accessory protein Nonstructural protein

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Molecular aspects of mers-cov

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Frontiers of Medicine 2017年第3期11卷 365-377页

作者： Ali A. Rabaan Ali M. Bazzi Shamsah H. Al-Ahmed Jaffar A. Al-Tawfiq Molecular Diagnostic Laboratory Johns Hopkins Aramco HeaIthcare Dhahran 31311 Saudi Arabia Microbiology Laboratory JohnsHopkins Aramco Healthcare Dhahran 3131i Saudi Arabia Specialty Paediatric Medicine Qatif CentralHospitaL Qatif 32654 Saudi Arabia Specialty Internal Medicine Johns Hopkins Aramco Healthcare Dhahran 31311 Saudi Arabia Indiana University School of Medicine Indianapolis IN 46202 USA

Middle East respiratory syndrome coronavirus （mers-cov） is a betacoronavirus which can cause acute respiratory distress in humans and is associated with a relatively high mortality rate. Since it was first identified in a patient who died in a Jeddah hospital in 2012, the World Health Organization has been notified of 1735 laboratory-confirmed cases from 27 countries, including 628 deaths. Most cases have occurred in Saudi Arabia. mers-cov ancestors may be found in Old World bats of the Vespertilionidae family. After a proposed bat to camel switching event, transmission of mers-cov to humans is likely to have been the result of multiple zoonotic transfers from dromedary camels. Human-to-human transmission appears to require close contact with infected persons, with outbreaks mainly occurring in hospital environments. Outbreaks have been associated with inadequate infection prevention and control implementation, resulting in recommendations on basic and more advanced infection prevention and control measures by the World Health Organization, and issuing of government guidelines based on these recommendations in affected countries including Saudi Arabia. Evolutionary changes in the virus, particularly in the viral spike protein which mediates virus-host cell contact may potentially increase transmission of this virus. Efforts are on-going to identify specific evidence-based therapies or vaccines. The broad-spectrum antiviral nitazoxanide has been shown to have in vitro activity against mers-cov. Synthetic peptides and candidate vaccines based on regions of the spike protein have shown promise in rodent and non-human primate models. GLS-5300, a prophylactic DNA-plasmid vaccine encoding S protein, is the first mers-cov vaccine to be tested in humans, while monoclonal antibody, m336 has given promising results in animal models and has potential for use in outbreak situations.

关键词： mers-cov Saudi Arabia spike protein transmission evolution vaccine

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The structural and accessory proteins M,ORF 4a,ORF 4b,and ORF 5 of Middle East respiratory syndrome coronavirus(mers-cov)are potent interferon antagonists

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Protein & Cell 2013年第12期4卷 951-961页

作者： Yang Yang Ling Zhang Heyuan Geng Yao Deng Baoying Huang Yin Guo Zhengdong Zhao Wenjie Tan Ke y Laboratory of Medical Virology Ministry of HealthNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Institute of Materia Medica(IMM) Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Key Laboratory of Pathogen System Biology Ministry of HealthInstitute of Pathogen BiologyChinese Academy of Medical SciencesBeijing 100176China

The newly emerged Middle East respiratory syndrome coronavirus(mers-cov)is a highly pathogenic respira-tory virus with pathogenic mechanisms that may be driven by innate immune *** goal of this study is to characterize the expression of the structural(S,E,M,N)and accessory(ORF 3,ORF 4a,ORF 4b,ORF 5)proteins of mers-cov and to determine whether any of these pro-teins acts as an interferon *** structural and accessory protein-coding plasmids with an N-terminal HA tag were constructed and transiently transfected into cells,and their native expression and subcellular localiza-tion were assessed using Wes tern blotting and indirect immunofl *** ORF 4b demonstrated majorly nuclear localization,all of the other proteins demonstrated cytoplasmic *** addition,for the fi rst time,our experiments revealed that the M,ORF 4a,ORF 4b,and ORF 5 proteins are potent interferon *** exami-nation revealed that the ORF 4a protein of mers-cov has the most potential to counteract the antiviral effects of IFN via the inhibition of both the interferon production(IFN-βpromoter activity,IRF-3/7 and NF-κB activation)and ISRE promoter element signaling ***,our re-sults provide new insights into the function and pathogenic role of the structural and accessory proteins of mers-cov.

关键词： mers-cov structural proteins accessory proteins interferon antagonists

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Newcastle disease virus-based mers-cov candidate vaccine elicits high-level and lasting neutralizing antibodies in Bactrian camels

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Journal of Integrative Agriculture 2017年第10期16卷 2264-2273页

作者： LIU Ren-qiang GE Jin-ying WANG Jin-ling SHAO Yu ZHANG Hui-lei WANG Jin-liang WEN Zhi-yuan BU Zhi-gao State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research Institute Chinese Academy of Agricultural Sciences Harbin 150069 P.R.China College of Veterinary Medicine Inner Mongolia Agricultural University Hohhot 010018 P.R. China

Middle East respiratory syndrome coronavirus （mers-cov）, a member of the Coronavifidae family, is the causative pathogen for mers that is characterized by high fever, pneumonia, acute respiratory distress syndrome （ARDS）, as well as extrapul- monary manifestations. Currently, there are no approved treatment regimens or vaccines for mers. Here~ we generated recombinant nonvirulent Newcastle disease virus （NDV） LaSota strain expressing mers-cov S protein （designated as rLa- mers-S）, and evaluated its immunogenicity in mice and Bactrian camels. The results revealed that rLa-mers-S showed similar growth properties to those of LaSota in embryonated chicken eggs, while animal immunization studies showed that rLa-mers-S induced mers-cov neutralizing antibodies in mice and camels. Our findings suggest that recombinant rLa- mers-S may be a potential mers-cov veterinary vaccine candidate for camels and other animals affected by mers.

关键词： Newcastle disease virus mers-cov neutralizing antibodies camels

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中东呼吸综合症冠状病毒（mers-cov）ORF5的IRES活性研究

中东呼吸综合症冠状病毒（MERS-CoV）ORF5的IRES活性研究

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作者：卢紫欣南方医科大学

学位级别：硕士

研究背景和目的中东呼吸综合征(Middle East Respiratory Syndrome,mers)是由中东呼吸综合征冠状病毒引起的一种人畜共患病,可致人类严重急性呼吸道症状,与SARS、SARA-cov2相类似,同属于β冠状病毒属,具有高度致病的呼吸道传染病。本实... 详细信息

研究背景和目的中东呼吸综合征(Middle East Respiratory Syndrome,mers)是由中东呼吸综合征冠状病毒引起的一种人畜共患病,可致人类严重急性呼吸道症状,与SARS、SARA-cov2相类似,同属于β冠状病毒属,具有高度致病的呼吸道传染病。本实验室前期,在研究来自韩国入境的输入性mers患者的咽拭子样品中,发现mers-cov病毒序列ORF5-E蛋白存在缺失的变异体。深入研究发现克隆的ORF5基因难以在细胞内表达;ORF5(含有终止密码子)与EGFP融合后,可以观察到EGFP的表达,提示:ORF5基因可能含有类似于内部核糖体进入位点(IRES)的功能,但其作用机制需要进一步研究。因此,本研究对MRES ORF5蛋白的功能进行研究,利用ORF5的重组表达载体,通过预测模型,筛选影响二级结构的关键位点,改变其RNA二级结构,研究ORF5的二级结构与IRES功能活性间的关系。研究方法1、构建mers ORF5与pEGFP-N1融合的真核表达载体,荧光显微镜观察表达情况、Western Blot检测目的蛋白表达。2、Infusion同源重组克隆技术构建pCAGGS-EGFP与ORF5融合的双荧光素酶载体,检测目的基因IRES活性。3、采用RNAFold预测ORF5 RNA二级结构,定点突变技术改变RNA二级结构,探索ORF5 IRES功能活性影响关键位点。4、使用已构建好的mers ORF5-E-Renilla-EGFP表达载体,采用定点突变技术改变ORF5 RNA二级结构,双荧光素酶、Western Blot检测目的蛋白表达情况。研究结果1、构建真核表达ORF5-EGFP融合蛋白载体,对ORF5蛋白的一些位点进行移码、终止突变后,均可有EGFP融合蛋白的表达,提示ORF5蛋白具有启动与之相连蛋白翻译的功能。2、使用软件RNA Fold对ORF5 RNA二级结构进行结构预测,有三个重要的茎环结构,分别是茎环Ⅰ(氨基酸序列从第124位到第127位)、茎环Ⅱ(氨基酸序列从第155位到第157位)、茎环Ⅲ(氨基酸序列从第184位到第188位)。3、对ORF5 RNA进行同义密码突变,改变ORF5的二级结构茎环,通过双荧光素酶检测,发现可以明显改变ORF5的IRES活性。4、在模拟病毒模型pEGFP-5ERI载体上,改变对应位点的RNA二级结构后,通过双荧光素酶分析,明显降低E蛋白与Renilla蛋白融合表达。研究结论1、ORF5蛋白起着介导病毒蛋白翻译功能,类似于IRES的内部核糖体进入位点。2、mers ORF5的茎环结构影响着IRES活性。3、位于ORF5序列上茎环Ⅰ结构(氨基酸序列从第124位到第127位),可能是其IRES活性的重要部分。

关键词： mers-cov ORF5 IRES活性

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A novel luciferase immunosorbent assay performs better than a commercial enzyme-linked immunosorbent assay to detect mers-cov specific IgG in humans and animals

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Biosafety and Health 2019年第3期1卷 134-143页

作者： Wenling Wang Tianyu Wang Yao Deng Peihua Niu Ruhan A Jincun Zhao Malik Peiris Shixing Tang Wenjie Tan MHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChina CDCBeijing 102206China Guangdong Provincial Key Laboratory of Tropical Disease Research Department of EpidemiologySchool of Public HealthSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory DiseaseThe first Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510182China School of Public Health Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong Special Administrative Region Center for Biosafety Mega-science Chinese Academy of SciencesBeijing 100101China

The Middle East respiratory syndrome(mers)is a lethal zoonosis caused by mers coronavirus(mers-cov)and poses a significant threat to public health ***,a rapid,sensitive,and specific serologic test for detecting anti-mers-cov antibodies in both humans and animals is urgently needed for the successful management of this ***,we evaluated various novel luciferase immunosorbent assays(LISA)based on nucleocapsid protein(NP)as well as fragments derived from spike protein(S)including subunit 1(S1),N terminal domain(NTD),receptorbinding domain(RBD)and subunit 2(S2)of S for the detection of mers-cov-specific *** proteins,including nanoluciferase(NLuc)and various fragments derived from the NP or S protein of mers-cov,were expressed in human embryonic kidney 293 T *** that detected anti-mers-cov IgG were further developed using cell lysates expressing various fusion *** of human or animal samples infected with mers-cov were used to analyze the sensitivity and specificity of various LISAs in reference to a mers-cov RT-PCR,commercial S1-based ELISA,and pseudovirus particle neutralization test(ppNT).Our results showed that the S1-,RBD-,and NP-LISAs were more sensitive than the NTD-and S2-LISAs for the detection of anti-mers-cov ***,the S1-,RBD-,and NP-LISAs were more sensitive(by at least 16-fold)than the commercially available ***,the S1-,RBD-,and NPLISA specifically recognized anti-mers-cov IgG and did not cross-react with samples derived from other human cov(OC43,229E,HKU1,NL63)-infected *** importantly,these LISAs proved their applicability and reliability for detecting anti-mers-cov IgG in samples from camels,monkeys,and mice,among which the RBD-LISA exhibited excellent *** results of this study suggest that the novel mers-cov RBD-and S1-LISAs are highly effective platforms for the rapid and sensitive detection of anti-mers-cov IgG in human and animal *** assays have

关键词： Luciferase immunosorbent assay(LISA) mers-cov Serological IgG detection Samples of humans and animals

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Coronaviruses in pregnant women in Saudi Arabia:A systematic comparative review of mers-cov and SARS-cov-2

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Asian pacific Journal of Reproduction 2021年第3期10卷 97-101页

作者： Mazin Barry Magdoleen A.Barry Division of Infectious Diseases Department of MedicineCollege of MedicineKing Saud UniversityRiyadhSaudi Arabia Department of Obstetrics and Gynecology King Salman HospitalMinistry of HealthRiyadhSaudi Arabia

Objective:To compare the effects of coronaviruses,such as Middle East respiratory syndrome coronavirus(mers-cov)or coronavirus disease 2019(covID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-cov-2),on pregnant women in Saudi Arabia,and to understand the disease dynamics of these coronaviruses so as to konw how to provide care and management of infected pregnant women and ***:We conducted a systematic review of all published papers on mers-cov and SARS-cov-2 infections in pregnant women in Saudi Arabia to identify knowledge *** and exclusion criteria were based on the PRISMA *** search included all papers which were published between September 1,2012 and November 29,2020 on pregnant women with mers-cov and/or covID-19 in Saudi *** 26 papers screened,five were included in the ***:A total of 11 pregnant women with mers-cov and four with covID-19 were reported in Saudi Arabia in the medical literature during the review *** mean ages of the women were 33 and 31 years old for mers-cov and covID-19,*** and fetal mortality in cases of merscov were 35%and 30%,respectively,while no maternal or fetal mortalities were reported in covID-19 ***:Very limited data has emerged from Saudi Arabia on pregnant women mers-cov and *** such high mortality observed with mers-cov compared to covID-19,there is a need for greater reporting of cases to truly grasp the extent of these infections in pregnant women in a country where both coronaviruses are circulating.

关键词： mers-cov SARS-cov-2 covID-19 Pregnant women

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mers-cov调控非小细胞肺癌细胞A549补体系统抑制因子C4BPA的机制

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免疫学杂志 2020年第9期36卷 756-762页

作者：王颖张静内蒙古民族大学附属医院检验科通辽028000 兴安盟人民医院检验科乌兰浩特137400

目的探讨关于中东呼吸综合征-冠状病毒(middle east respiratory syndrome-coronavirus,mers-cov)调控非小细胞肺癌细胞A549补体系统抑制因子补体成分4结合蛋白Alpha(complement component 4 binding protein alpha,C4BPA)的机制。方法以是否mers-cov感染非小细胞肺癌细胞A549分为感染组和对照组,通过酶联免疫吸附试验(ELISA)、免疫印迹和实时荧光定量PCR(qPCR)分别检测2组细胞C4BPA的蛋白和mRNA表达情况。TargetScanHuman预测与C4BPA结合的miRNA,实时荧光定量PCR和荧光素酶报告试验确定靶向C4BPA的miRNA。在mers-cov感染的情况下,过表达或敲低靶向C4BPA的miRNA,ELISA或qPCR检测C4BPA的表达和分泌情况。同时分析人肺成纤维细胞和小鼠感染mers-cov后,C4BPA和miR-451b的表达情况。结果非小细胞肺癌细胞A549感染mers-cov后,其分泌的C4BPA增加(Pmers-cov抑制非小细胞肺癌细胞A549 miR-451b的表达(Pmers-cov感染人肺成纤维细胞和小鼠后,miR-451b的表达受到抑制(Pmerscov感染引起的C4BPA增多能够抑制补体经典系统的溶血活性。结论mers-cov通过下调miR-451b促进C4BPA的分泌。

关键词： mers-cov 非小细胞肺癌细胞A549 C4BPA miR-451b

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mers-cov E蛋白诱导293T细胞自噬的研究

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中国病原生物学杂志 2020年第9期15卷 997-1004页

作者：周烨真高静黄姗蔡金泰朱慧敏陆维智曹观华张宝南方医科大学公共卫生学院三级生物安全实验室广东广州510515

目的本研究旨在探讨中东呼吸综合征冠状病毒包膜蛋白(mers-cov E蛋白)诱导293T细胞自噬其及作用机制。方法构建表达载体pEGFP-E、pEGFP-ERT、pEGFP-ORF5-E,分别将其转染293T细胞,采用荧光显微镜和Western blot方法检测目的蛋白的表达,采... 详细信息

目的本研究旨在探讨中东呼吸综合征冠状病毒包膜蛋白(mers-cov E蛋白)诱导293T细胞自噬其及作用机制。方法构建表达载体pEGFP-E、pEGFP-ERT、pEGFP-ORF5-E,分别将其转染293T细胞,采用荧光显微镜和Western blot方法检测目的蛋白的表达,采用Western blot方法检测LC3的表达量,采用Real-time PCR(RT-PCR)和Western blot方法检测自噬相关基因Atg4,Atg5,Atg7,P62,PI3KC3的表达情况。结果成功构建pEGFP-E、pEGFP-ERT、pEGFP-ORF5-E表达载体,在293T细胞中可检测到目的蛋白的表达。转染后24 h,与阴性对照组相比,pEGFP-E实验组LC3 II的表达量显著高于转染pEGFP-N1阴性对照组(P0.05),这表明在293T细胞中过表达mers-cov E蛋白能增加LC3 II的表达,但并不引起自噬相关基因转录和相应蛋白表达水平的变化。结论mers-cov E蛋白可诱导293T细胞自噬,其机制不依赖于Atg蛋白。

关键词： mers-cov E蛋白自噬 Atg蛋白

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