In- 2012 Middle-East respiratory syn-drome coron-avirus(MERS-CoV) was evolved in- the Arabian- Pen-in-sula. Tre-men-dous an-d successful efforts have been- con-ducted to discover the gen-ome structure, epidemiology, c...In- 2012 Middle-East respiratory syn-drome coron-avirus(MERS-CoV) was evolved in- the Arabian- Pen-in-sula. Tre-men-dous an-d successful efforts have been- con-ducted to discover the gen-ome structure, epidemiology, clin-ical sign-s, pathogen-esis, diagn-osis an-d an-tiviral therapy. Taphozous perforatus bats are the in-crimin-ated reservoir host and camels are the currently confirmed an-imal lin-ker. The virus resulted in- less than- 1000 in-fected cases an-d 355 deaths. The case fatality rate of the MERS-Co V is high, however, man-y survivors of MERS-CoV in-fection- showed in-apparen-t in-fection-s an-d, in- several cases, multiple co-in-fectin-g agen-ts did exist. Although MERS-CoV appears to be a dan-gerous disease, it is argued here that a full assessmen-t of curren-t kn-owledge about the disease does n-ot suggest that it is a truly scary killer.展开更多
The papain-like protease(PL^(pro)) of Middle-East respiratory syndrome coronavirus(MERS-CoV) has proteolytic,deubiquitinating,and de ISGylating activities.The latter two are involved in the suppression of the antivira...The papain-like protease(PL^(pro)) of Middle-East respiratory syndrome coronavirus(MERS-CoV) has proteolytic,deubiquitinating,and de ISGylating activities.The latter two are involved in the suppression of the antiviral innate immune response of the host cell.To contribute to an understanding of this process,we present here the X-ray crystal structure of a complex between MERS-CoV PL^(pro) and human ubiquitin(Ub) that is devoid of any covalent linkage between the two proteins.Five regions of the PL^(pro) bind to two areas of the Ub.The C-terminal five residues of Ub,RLRGG,are similar to the P5–P1 residues of the polyprotein substrates of the PL^(pro) and are responsible for the major part of the interaction between the two macromolecules.Through sitedirected mutagenesis,we demonstrate that conserved Asp165 and non-conserved Asp164 are important for the catalytic activities of MERS-CoV PL^(pro).The enzyme appears not to be optimized for catalytic efficiency; thus,replacement of Phe269 by Tyr leads to increased peptidolytic and deubiquitinating activities.Ubiquitin binding by MERS-CoV PL^(pro) involves remarkable differences compared to the corresponding complex with SARS-CoV PL^(pro).The structure and the mutational study help understand common and unique features of the deubiquitinating activity of MERS-CoV PL^(pro).展开更多
We describe the first genome isolation of Middle East respiratory syndrome coronavirus(MERS-CoV) in Kenya. This fatal zoonotic pathogen was first described in the Kingdom of Saudi Arabia in 2012. Epidemiological and m...We describe the first genome isolation of Middle East respiratory syndrome coronavirus(MERS-CoV) in Kenya. This fatal zoonotic pathogen was first described in the Kingdom of Saudi Arabia in 2012. Epidemiological and molecular evidence revealed zoonotic transmission from camels to humans and between humans. Currently, MERS-CoV is classified by the WHO as having high pandemic potential requiring greater surveillance. Previous studies of MERS-CoV in Kenya mainly focused on site-specific and archived camel and human serum samples for antibodies. We conducted active nationwide cross-sectional surveillance of camels and humans in Kenya, targeting both nasal swabs and plasma samples from 1,163 camels and 486 humans collected from January 2016 to June 2018. A total of 792 camel plasma samples were positive by ELISA. Seroprevalence increased with age, and the highest prevalence was observed in adult camels(82.37%, 95%confidence interval(CI) 79.50–84.91). More female camels were significantly seropositive(74.28%, 95% CI 71.14–77.19)than male camels(P \ 0.001)(53.74%, 95% CI 48.48–58.90). Only 11 camel nasal swabs were positive for MERS-CoV by reverse transcription-quantitative PCR. Phylogenetic analysis of whole genome sequences showed that Kenyan MERSCoV clustered within sub-clade C2, which is associated with the African clade, but did not contain signature deletions of orf4 b in African viruses. None of the human plasma screened contained neutralizing antibodies against MERS-CoV. This study confirms the geographically widespread occurrence of MERS-CoV in Kenyan camels. Further one-health surveillance approaches in camels, wildlife, and human populations are needed.展开更多
The emergence of Middle East respiratory syndrome coronavirus （MERS-CoV） in 2012 brought back memories of the occurrence of severe acute respiratory syndrome coronavirus （SARS-CoV） in 2002. More than 1500 MERS-CoV...The emergence of Middle East respiratory syndrome coronavirus （MERS-CoV） in 2012 brought back memories of the occurrence of severe acute respiratory syndrome coronavirus （SARS-CoV） in 2002. More than 1500 MERS-CoV cases were recorded in 42 months with a case fatality rate （CFR） of 40%. Meanwhile, 8000 cases of SARS-CoV were confirmed in six months with a CFR of 10%. The clinical presentation of MERS-CoV ranges from mild and non-specific presentation to progressive and severe pneumonia. No predictive signs or symptoms exist to differentiate MERS-CoV from community-acquired pneumonia in hospitalized patients. An apparent heterogeneity was observed in transmission. Most MERS-CoV cases were secondary to large outbreaks in healthcare settings. These cases were secondary to community-acquired cases, which may also cause family outbreaks. Travel-associated MERS infection remains low. However, the virus exhibited a clear tendency to cause large outbreaks outside the Arabian Peninsula as exemplified by the outbreak in the Republic of Korea. In this review, we summarize the current knowledge about MERS-CoV and highlight travel-related issues.展开更多
As an effort to understand the effect of diabetes on the increasing rate of COVID-19 infection, we embarked upon a detailed statistical analysis of various datasets that include COVID-19 infection and mortality rate, ...As an effort to understand the effect of diabetes on the increasing rate of COVID-19 infection, we embarked upon a detailed statistical analysis of various datasets that include COVID-19 infection and mortality rate, diabetes and diseases that may contribute to the severity and risk factor of diabetes in individuals and this impact on COVID-19 and the mortality rate. These diseases include respiratory diseases, cardiovascular diseases, and obesity. Equally significant is the statistical analysis on ethnicity, age, and sex on COVID-19 infection as well as mortality rate. Their possible contributions to increasing the severity and risk factor of diabetes as a risk to mortality to individuals who have COVID-19. Objectives: The ultimate objectives of this investigation are as follow: 1) Is there a risk factor of diabetes on COVID-19 infection and increasing mortality rate? 2) To what extent do other disease conditions that include, obesity, heart failure, and respiratory diseases influence the severity and risk factor of diabetes on increasing COVID-19 infection and mortality rate? 3) To what extent does age, race, and gender increase the mortality of COVID-19 and increase the severity and risk factor of diabetes on COVID-19 mortality rate? 4) How and why COVID-19 virus increases the risk of diabetes in children? 5) Diabetes and COVID-19: Who is most at Risk? Lastly, understanding the misconception of COVID-19 and diabetes.展开更多
中东呼吸综合征(Middle East respiratory syndrome,MERS)是由一种新型冠状病毒引起的呼吸系统疾病,2012年首次报道,病死率较高,且近年来发病例数明显上升,范围也逐步扩大,引起了广泛的关注。2015年5月26日,中国出现了首例输入性MERS病...中东呼吸综合征(Middle East respiratory syndrome,MERS)是由一种新型冠状病毒引起的呼吸系统疾病,2012年首次报道,病死率较高,且近年来发病例数明显上升,范围也逐步扩大,引起了广泛的关注。2015年5月26日,中国出现了首例输入性MERS病例,建立相应的防控体系刻不容缓。作者对目前MERS的流行现状进行概述,结合"One Heal"理念,阐述针对MERS等人兽共患病的防控策略,为新发传染病的防控提供新的思路。展开更多
中东呼吸综合征(Middle East Respiratory Syndrome,MERS)冠状病毒是一种新型冠状病毒,主要通过感染的动物或人传播给人。该病毒感染能引起急性呼吸衰竭、多器官功能衰竭,甚至危及生命。本文从MERS的流行现况、病原学、流行病学和预防控...中东呼吸综合征(Middle East Respiratory Syndrome,MERS)冠状病毒是一种新型冠状病毒,主要通过感染的动物或人传播给人。该病毒感染能引起急性呼吸衰竭、多器官功能衰竭,甚至危及生命。本文从MERS的流行现况、病原学、流行病学和预防控制4个方面的最新研究进展作一综述,旨在为该病的预防与控制提供参考。展开更多
中东呼吸综合征冠状病毒(Middle East Respiratory Syndrome-Coronavirus,MERS-CoV)是继SARS冠状病毒(SARS-CoV)之后发现的一种能引起人严重急性呼吸道疾病且具有高致死率的新型病毒。目前还没有有效的抗病毒治疗药物或疫苗。现已从主...中东呼吸综合征冠状病毒(Middle East Respiratory Syndrome-Coronavirus,MERS-CoV)是继SARS冠状病毒(SARS-CoV)之后发现的一种能引起人严重急性呼吸道疾病且具有高致死率的新型病毒。目前还没有有效的抗病毒治疗药物或疫苗。现已从主要流行的中东地区逐渐蔓延至多个国家,具有全球流行的潜在趋势,引起了世界各国的极大关注及众多的调查研究。本文主要对MERS-CoV的传播源及途径、致病机理和抗病毒药物及疫苗等的研究进展做一综述,以期对研制特异的抗病毒药物及疫苗和实施切实有效的预防及控制措施提供参考。展开更多
Coronaviruses are among the largest group of known positive-sense RNA viruses with a wide range of animal hosts as reservoir. In the last two decades,newly evolved coronaviruses such as the severe acute respiratory sy...Coronaviruses are among the largest group of known positive-sense RNA viruses with a wide range of animal hosts as reservoir. In the last two decades,newly evolved coronaviruses such as the severe acute respiratory syndrome coronavirus(SARS-CoV) which caused the infamous 2002 outbreak, the Middle East respiratory syndrome coronavirus(MERS-CoV) which caused an outbreak in 2012, and now the SARS-CoV-2 [responsible for the current coronavirus disease 2019(COVID-19)] have all posed notable threats to global public health.But, how does the current COVID-19 outbreak compare with previous coronaviruses diseases? In this review, we look at the key differences between SARS-CoV, MERS-CoV, and SARS-CoV-2, and examine challenges in determining accurate estimates of the severity of COVID-19. We discuss coronavirus outbreaks in light of key outbreak severity indicators including,disease fatality, pathogen novelty, ease of transmission, geographical range, and outbreak preparedness. Finally, we review clinical trials of emerging treatment modalities and provide recommendations on the control of COVID-19 based on the mode of transmission of the coronaviruses. We also recommend the development and use of a standardized predictive epidemic severity models to inform future epidemic response.展开更多
文摘In- 2012 Middle-East respiratory syn-drome coron-avirus(MERS-CoV) was evolved in- the Arabian- Pen-in-sula. Tre-men-dous an-d successful efforts have been- con-ducted to discover the gen-ome structure, epidemiology, clin-ical sign-s, pathogen-esis, diagn-osis an-d an-tiviral therapy. Taphozous perforatus bats are the in-crimin-ated reservoir host and camels are the currently confirmed an-imal lin-ker. The virus resulted in- less than- 1000 in-fected cases an-d 355 deaths. The case fatality rate of the MERS-Co V is high, however, man-y survivors of MERS-CoV in-fection- showed in-apparen-t in-fection-s an-d, in- several cases, multiple co-in-fectin-g agen-ts did exist. Although MERS-CoV appears to be a dan-gerous disease, it is argued here that a full assessmen-t of curren-t kn-owledge about the disease does n-ot suggest that it is a truly scary killer.
基金supported by the European Commission through its "SILVER" project (contract no.HEALTHF3-2010-260644)the German Center for Infection Research (DZIF)support by the DFG Cluster of Excellence "Inflammation at Interfaces" (EXC 306)
文摘The papain-like protease(PL^(pro)) of Middle-East respiratory syndrome coronavirus(MERS-CoV) has proteolytic,deubiquitinating,and de ISGylating activities.The latter two are involved in the suppression of the antiviral innate immune response of the host cell.To contribute to an understanding of this process,we present here the X-ray crystal structure of a complex between MERS-CoV PL^(pro) and human ubiquitin(Ub) that is devoid of any covalent linkage between the two proteins.Five regions of the PL^(pro) bind to two areas of the Ub.The C-terminal five residues of Ub,RLRGG,are similar to the P5–P1 residues of the polyprotein substrates of the PL^(pro) and are responsible for the major part of the interaction between the two macromolecules.Through sitedirected mutagenesis,we demonstrate that conserved Asp165 and non-conserved Asp164 are important for the catalytic activities of MERS-CoV PL^(pro).The enzyme appears not to be optimized for catalytic efficiency; thus,replacement of Phe269 by Tyr leads to increased peptidolytic and deubiquitinating activities.Ubiquitin binding by MERS-CoV PL^(pro) involves remarkable differences compared to the corresponding complex with SARS-CoV PL^(pro).The structure and the mutational study help understand common and unique features of the deubiquitinating activity of MERS-CoV PL^(pro).
基金funded by Sino-Africa Joint Research Center (SAJC201313 and SAJC201605)External Cooperation Program of CAS (153211KYSB20160001)National Science and Technology Major Project (2018ZX0101004)
文摘We describe the first genome isolation of Middle East respiratory syndrome coronavirus(MERS-CoV) in Kenya. This fatal zoonotic pathogen was first described in the Kingdom of Saudi Arabia in 2012. Epidemiological and molecular evidence revealed zoonotic transmission from camels to humans and between humans. Currently, MERS-CoV is classified by the WHO as having high pandemic potential requiring greater surveillance. Previous studies of MERS-CoV in Kenya mainly focused on site-specific and archived camel and human serum samples for antibodies. We conducted active nationwide cross-sectional surveillance of camels and humans in Kenya, targeting both nasal swabs and plasma samples from 1,163 camels and 486 humans collected from January 2016 to June 2018. A total of 792 camel plasma samples were positive by ELISA. Seroprevalence increased with age, and the highest prevalence was observed in adult camels(82.37%, 95%confidence interval(CI) 79.50–84.91). More female camels were significantly seropositive(74.28%, 95% CI 71.14–77.19)than male camels(P \ 0.001)(53.74%, 95% CI 48.48–58.90). Only 11 camel nasal swabs were positive for MERS-CoV by reverse transcription-quantitative PCR. Phylogenetic analysis of whole genome sequences showed that Kenyan MERSCoV clustered within sub-clade C2, which is associated with the African clade, but did not contain signature deletions of orf4 b in African viruses. None of the human plasma screened contained neutralizing antibodies against MERS-CoV. This study confirms the geographically widespread occurrence of MERS-CoV in Kenyan camels. Further one-health surveillance approaches in camels, wildlife, and human populations are needed.
文摘The emergence of Middle East respiratory syndrome coronavirus （MERS-CoV） in 2012 brought back memories of the occurrence of severe acute respiratory syndrome coronavirus （SARS-CoV） in 2002. More than 1500 MERS-CoV cases were recorded in 42 months with a case fatality rate （CFR） of 40%. Meanwhile, 8000 cases of SARS-CoV were confirmed in six months with a CFR of 10%. The clinical presentation of MERS-CoV ranges from mild and non-specific presentation to progressive and severe pneumonia. No predictive signs or symptoms exist to differentiate MERS-CoV from community-acquired pneumonia in hospitalized patients. An apparent heterogeneity was observed in transmission. Most MERS-CoV cases were secondary to large outbreaks in healthcare settings. These cases were secondary to community-acquired cases, which may also cause family outbreaks. Travel-associated MERS infection remains low. However, the virus exhibited a clear tendency to cause large outbreaks outside the Arabian Peninsula as exemplified by the outbreak in the Republic of Korea. In this review, we summarize the current knowledge about MERS-CoV and highlight travel-related issues.
文摘As an effort to understand the effect of diabetes on the increasing rate of COVID-19 infection, we embarked upon a detailed statistical analysis of various datasets that include COVID-19 infection and mortality rate, diabetes and diseases that may contribute to the severity and risk factor of diabetes in individuals and this impact on COVID-19 and the mortality rate. These diseases include respiratory diseases, cardiovascular diseases, and obesity. Equally significant is the statistical analysis on ethnicity, age, and sex on COVID-19 infection as well as mortality rate. Their possible contributions to increasing the severity and risk factor of diabetes as a risk to mortality to individuals who have COVID-19. Objectives: The ultimate objectives of this investigation are as follow: 1) Is there a risk factor of diabetes on COVID-19 infection and increasing mortality rate? 2) To what extent do other disease conditions that include, obesity, heart failure, and respiratory diseases influence the severity and risk factor of diabetes on increasing COVID-19 infection and mortality rate? 3) To what extent does age, race, and gender increase the mortality of COVID-19 and increase the severity and risk factor of diabetes on COVID-19 mortality rate? 4) How and why COVID-19 virus increases the risk of diabetes in children? 5) Diabetes and COVID-19: Who is most at Risk? Lastly, understanding the misconception of COVID-19 and diabetes.
文摘中东呼吸综合征(Middle East respiratory syndrome,MERS)是由一种新型冠状病毒引起的呼吸系统疾病,2012年首次报道,病死率较高,且近年来发病例数明显上升,范围也逐步扩大,引起了广泛的关注。2015年5月26日,中国出现了首例输入性MERS病例,建立相应的防控体系刻不容缓。作者对目前MERS的流行现状进行概述,结合"One Heal"理念,阐述针对MERS等人兽共患病的防控策略,为新发传染病的防控提供新的思路。
文摘中东呼吸综合征(Middle East Respiratory Syndrome,MERS)冠状病毒是一种新型冠状病毒,主要通过感染的动物或人传播给人。该病毒感染能引起急性呼吸衰竭、多器官功能衰竭,甚至危及生命。本文从MERS的流行现况、病原学、流行病学和预防控制4个方面的最新研究进展作一综述,旨在为该病的预防与控制提供参考。
文摘中东呼吸综合征冠状病毒(Middle East Respiratory Syndrome-Coronavirus,MERS-CoV)是继SARS冠状病毒(SARS-CoV)之后发现的一种能引起人严重急性呼吸道疾病且具有高致死率的新型病毒。目前还没有有效的抗病毒治疗药物或疫苗。现已从主要流行的中东地区逐渐蔓延至多个国家,具有全球流行的潜在趋势,引起了世界各国的极大关注及众多的调查研究。本文主要对MERS-CoV的传播源及途径、致病机理和抗病毒药物及疫苗等的研究进展做一综述,以期对研制特异的抗病毒药物及疫苗和实施切实有效的预防及控制措施提供参考。
文摘Coronaviruses are among the largest group of known positive-sense RNA viruses with a wide range of animal hosts as reservoir. In the last two decades,newly evolved coronaviruses such as the severe acute respiratory syndrome coronavirus(SARS-CoV) which caused the infamous 2002 outbreak, the Middle East respiratory syndrome coronavirus(MERS-CoV) which caused an outbreak in 2012, and now the SARS-CoV-2 [responsible for the current coronavirus disease 2019(COVID-19)] have all posed notable threats to global public health.But, how does the current COVID-19 outbreak compare with previous coronaviruses diseases? In this review, we look at the key differences between SARS-CoV, MERS-CoV, and SARS-CoV-2, and examine challenges in determining accurate estimates of the severity of COVID-19. We discuss coronavirus outbreaks in light of key outbreak severity indicators including,disease fatality, pathogen novelty, ease of transmission, geographical range, and outbreak preparedness. Finally, we review clinical trials of emerging treatment modalities and provide recommendations on the control of COVID-19 based on the mode of transmission of the coronaviruses. We also recommend the development and use of a standardized predictive epidemic severity models to inform future epidemic response.
