共查询到20条相似文献,搜索用时 187 毫秒
1.
Musa A. Garbati Shamsudeen F. Fagbo Vicky J. Fang Leila Skakni Mercy Joseph Tariq A. Wani Benjamin J. Cowling Malik Peiris Ahmed Hakawi 《PloS one》2016,11(11)
Middle East Respiratory syndrome (MERS) first emerged in Saudi Arabia in 2012 and remains a global health concern. The objective of this study was to compare the clinical features and risk factors for adverse outcome in patients with RT-PCR confirmed MERS and in those with acute respiratory disease who were MERS-CoV negative, presenting to the King Fahad Medical City (KFMC) in Riyadh between October 2012 and May 2014. The demographics, clinical and laboratory characteristics and clinical outcomes of patients with RT-PCR confirmed MERS-CoV infection was compared with those testing negative MERS-CoV PCR. Health care workers (HCW) with MERS were compared with MERS patients who were not health care workers. One hundred and fifty nine patients were eligible for inclusion. Forty eight tested positive for MERS CoV, 44 (92%) being hospital acquired infections and 23 were HCW. There were 111 MERS-CoV negative patients with acute respiratory illnesses included in this study as “negative controls”. Patient with confirmed MERS-CoV infection were not clinically distinguishable from those with negative MERS-CoV RT-PCR results although diarrhoea was commoner in MERS patients. A high level of suspicion in initiating laboratory tests for MERS-CoV is therefore indicated. Variables associated with adverse outcome were older age and diabetes as a co-morbid illness. Interestingly, co-morbid illnesses other than diabetes were not significantly associated with poor outcome. Health care workers with MERS had a markedly better clinical outcome compared to non HCW MERS patients. 相似文献
2.
Lanying Du Zhihua Kou Cuiqing Ma Xinrong Tao Lili Wang Guangyu Zhao Yaoqing Chen Fei Yu Chien-Te K. Tseng Yusen Zhou Shibo Jiang 《PloS one》2013,8(12)
An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367–606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients’ lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection. 相似文献
3.
Middle-East Respiratory Syndrome coronavirus (MERS-CoV) was identified to cause severe respiratory infection in humans since 2012. The continuing MERS epidemic with a case-fatality of more than 30 % poses a major threat to public health worldwide. Currently, the pathogenesis of human MERS-CoV infection remains poorly understood. We reviewed experimental findings from human primary cells and ex vivo human lung tissues, as well as those from animal studies, so as to understand the pathogenesis and high case-fatality of MERS. Human respiratory epithelial cells are highly susceptible to MERS-CoV and can support productive viral replication. However, the induction of antiviral cytokines and proinflammatory cytokines/chemokines are substantially dampened in the infected epithelial cells, due to the antagonistic mechanisms evolved by the virus. MERS-CoV can readily infect and robustly replicate in human macrophages and dendritic cells, triggering the aberrant production of proinflammatory cytokines/chemokines. MERS-CoV can also effectively infect human primary T cells and induce massive apoptosis in these cells. Although data from clinical, in vitro and ex vivo studies suggested the potential for virus dissemination, extrapulmonary involvement in MERS patients has not been ascertained due to the lack of autopsy study. In MERS-CoV permissive animal models, although viral RNA can be detected from multiple organs of the affected animals, the brain of human DPP4-transgenic mouse was the only extrapulmonary organ from which the infectious virus can be recovered. More research findings on the pathogenesis of MERS and the tissue tropisms of MERS-CoV may help to improve the treatment and infection control of MERS. 相似文献
4.
Somayeh Shokri Shahab Mahmoudvand Reza Taherkhani Fatemeh Farshadpour 《Journal of cellular physiology》2019,234(3):2143-2151
Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. In 2012, a new human disease called Middle East respiratory syndrome (MERS) emerged in the Middle East. MERS was caused by a virus that was originally called human coronavirus-Erasmus Medical Center/2012 but was later renamed as Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV causes high fever, cough, acute respiratory tract infection, and multiorgan dysfunction that may eventually lead to the death of the infected individuals. The exact origin of MERS-CoV remains unknown, but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host, from which human infections may sporadically occur through the zoonotic transmission. Human to human transmission also occurs in healthcare facilities and communities. Recent studies on Middle Eastern respiratory continue to highlight the need for further understanding the virus-host interactions that govern disease severity and infection outcome. In this review, we have highlighted the major mechanisms of immune evasion strategies of MERS-CoV. We have demonstrated that M, 4a, 4b proteins and Plppro of MERS-CoV inhibit the type I interferon (IFN) and nuclear factor-κB signaling pathways and therefore facilitate innate immune evasion. In addition, nonstructural protein 4a (NSP4a), NSP4b, and NSP15 inhibit double-stranded RNA sensors. Therefore, the mentioned proteins limit early induction of IFN and cause rapid apoptosis of macrophages. MERS-CoV strongly inhibits the activation of T cells with downregulation of antigen presentation. In addition, uncontrolled secretion of interferon ɣ-induced protein 10 and monocyte chemoattractant protein-1 can suppress proliferation of human myeloid progenitor cells. 相似文献
5.
《Cell calcium》2018
Middle East Respiratory Syndrome coronavirus (MERS-CoV) infections are associated with a significant mortality rate, and existing drugs show poor efficacy. Identifying novel targets/pathways required for MERS infectivity is therefore important for developing novel therapeutics. As an enveloped virus, translocation through the endolysosomal system provides one pathway for cellular entry of MERS-CoV. In this context, Ca2+-permeable channels within the endolysosomal system regulate both the luminal environment and trafficking events, meriting investigation of their role in regulating processing and trafficking of MERS-CoV. Knockdown of endogenous two-pore channels (TPCs), targets for the Ca2+ mobilizing second messenger NAADP, impaired infectivity in a MERS-CoV spike pseudovirus particle translocation assay. This effect was selective as knockdown of the lysosomal cation channel mucolipin-1 (TRPML1) was without effect. Pharmacological inhibition of NAADP-evoked Ca2+ release using several bisbenzylisoquinoline alkaloids also blocked MERS pseudovirus translocation. Knockdown of TPC1 (biased endosomally) or TPC2 (biased lysosomally) decreased the activity of furin, a protease which facilitates MERS fusion with cellular membranes. Pharmacological or genetic inhibition of TPC1 activity also inhibited endosomal motility impairing pseudovirus progression through the endolysosomal system. Overall, these data support a selective, spatially autonomous role for TPCs within acidic organelles to support MERS-CoV translocation. 相似文献
6.
Little is known about the biology of the emerging human group c betacoronavirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV). Because coronavirus spike glycoproteins (S) mediate virus entry, affect viral host range, and elicit neutralizing antibodies, analyzing the functions of MERS-CoV S protein is a high research priority. MERS-CoV S on lentivirus pseudovirions mediated entry into a variety of cell types including embryo cells from New World Eptesicus fuscus bats. Surprisingly, a polyclonal antibody to the S protein of MHV, a group a murine betacoronavirus, cross-reacted in immunoblots with the S2 domain of group c MERS-CoV spike protein. MERS pseudovirions released from 293T cells contained only uncleaved S, and pseudovirus entry was blocked by lysosomotropic reagents NH4Cl and bafilomycin and inhibitors of cathepsin L. However, when MERS pseudovirions with uncleaved S protein were adsorbed at 4°C to Vero E6 cells, brief trypsin treatment at neutral pH triggered virus entry at the plasma membrane and syncytia formation. When 293T cells producing MERS pseudotypes co-expressed serine proteases TMPRSS-2 or -4, large syncytia formed at neutral pH, and the pseudovirions produced were non-infectious and deficient in S protein. These experiments show that if S protein on MERS pseudovirions is uncleaved, then viruses enter by endocytosis in a cathepsin L-dependent manner, but if MERS-CoV S is cleaved, either during virus maturation by serine proteases or on pseudovirions by trypsin in extracellular fluids, then viruses enter at the plasma membrane at neutral pH and cause massive syncytia formation even in cells that express little or no MERS-CoV receptor. Thus, whether MERS-CoV enters cells within endosomes or at the plasma membrane depends upon the host cell type and tissue, and is determined by the location of host proteases that cleave the viral spike glycoprotein and activate membrane fusion. 相似文献
8.
《Saudi Journal of Biological Sciences》2016,23(4):507-511
Numerous viral infections have arisen and affected global healthcare facilities. Millions of people are at severe risk of acquiring several evolving viral infections through several factors. In the present article we have described about risk factors, chance of infection, and prevention methods of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV), human coronaviruses (CoVs) frequently cause a normal cold which is mild and self-restricting. Zoonotic transmission of CoVs such as the newly discovered MERS-CoV and SARS-CoV, may be associated with severe lower respiratory tract infection. The present review provides the recent clinical and pathological information on MERS and SARS. The task is to transform these discoveries about MERS and SARS pathogenesis and to develop intervention methods that will eventually allow the effective control of these recently arising severe viral infections. Global health sector has learnt many lessons through the recent outbreak of MERS and SARS, but the need for identifying new antiviral treatment was not learned. In the present article we have reviewed the literature on the several facets like transmission, precautions and effectiveness of treatments used in patients with MERS-CoV and SARS infections. 相似文献
9.
正Dear Editor,Middle East respiratory syndrome coronavirus (MERS-CoV), first isolated in 2012, has emerged zoonotically among humans (van Boheemen et al. 2012). Since then,MERS-CoV continues to be a public health concern, with a fatality rate of 35%. On-going MERS-CoV outbreaks highlight the urgent need for the development of inter- 相似文献
10.
Sharon L. Deem Eric M. Fèvre Margaret Kinnaird A. Springer Browne Dishon Muloi Gert-Jan Godeke Marion Koopmans Chantal B. Reusken 《PloS one》2015,10(10)
Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently identified virus causing severe viral respiratory illness in people. Little is known about the reservoir in the Horn of Africa. In Kenya, where no human MERS cases have been reported, our survey of 335 dromedary camels, representing nine herds in Laikipia County, showed a high seroprevalence (46.9%) to MERS-CoV antibodies. Between herd differences were present (14.3%– 82.9%), but was not related to management type or herd isolation. Further research should focus on identifying similarity between MERS-CoV viral isolates in Kenya and clinical isolates from the Middle East and elsewhere. 相似文献
11.
12.
Kei Ohnuma Bart L. Haagmans Ryo Hatano V. Stalin Raj Huihui Mou Satoshi Iwata Nam H. Dang Berend Jan Bosch Chikao Morimoto 《Journal of virology》2013,87(24):13892-13899
We identified the domains of CD26 involved in the binding of Middle East respiratory syndrome coronavirus (MERS-CoV) using distinct clones of anti-CD26 monoclonal antibodies (MAbs). One clone, named 2F9, almost completely inhibited viral entry. The humanized anti-CD26 MAb YS110 also significantly inhibited infection. These findings indicate that both 2F9 and YS110 are potential therapeutic agents for MERS-CoV infection. YS110, in particular, is a good candidate for immediate testing as a therapeutic modality for MERS. 相似文献
13.
Interactions of SARS-CoV-2 and MERS-CoV fusion peptides measured using single-molecule force methods
《Biophysical journal》2023,122(4):646-660
We address the challenge of understanding how hydrophobic interactions are encoded by fusion peptide (FP) sequences within coronavirus (CoV) spike proteins. Within the FPs of severe acute respiratory syndrome CoV 2 and Middle East respiratory syndrome CoV (MERS-CoV), a largely conserved peptide sequence called FP1 (SFIEDLLFNK and SAIEDLLFDK in SARS-2 and MERS, respectively) has been proposed to play a key role in encoding hydrophobic interactions that drive viral-host cell membrane fusion. Although a non-polar triad (Leu-Leu-Phe (LLF)) is common to both FP1 sequences, and thought to dominate the encoding of hydrophobic interactions, FP1 from SARS-2 and MERS differ in two residues (Phe 2 versus Ala 2 and Asn 9 versus Asp 9, respectively). Here we explore whether single-molecule force measurements can quantify hydrophobic interactions encoded by FP1 sequences, and then ask whether sequence variations between FP1 from SARS-2 and MERS lead to significant differences in hydrophobic interactions. We find that both SARS-2 and MERS wild-type FP1 generate measurable hydrophobic interactions at the single-molecule level, but that SARS-2 FP1 encodes a substantially stronger hydrophobic interaction than its MERS counterpart (1.91 ± 0.03 nN versus 0.68 ± 0.03 nN, respectively). By performing force measurements with FP1 sequences with single amino acid substitutions, we determine that a single-residue mutation (Phe 2 versus Ala 2) causes the almost threefold difference in the hydrophobic interaction strength generated by the FP1 of SARS-2 versus MERS, despite the presence of LLF in both sequences. Infrared spectroscopy and circular dichroism measurements support the proposal that the outsized influence of Phe 2 versus Ala 2 on the hydrophobic interaction arises from variation in the secondary structure adopted by FP1. Overall, these insights reveal how single-residue diversity in viral FPs, including FP1 of SARS-CoV-2 and MERS-CoV, can lead to substantial changes in intermolecular interactions proposed to play a key role in viral fusion, and hint at strategies for regulating hydrophobic interactions of peptides in a range of contexts. 相似文献
14.
Background
MERS-CoV is a newly emerged human coronavirus reported closely related with HKU4 and HKU5 Bat coronaviruses. Bat and MERS corona-viruses are structurally related. Therefore, it is of interest to estimate the degree of conserved antigenic sites among them. It is of importance to elucidate the shared antigenic-sites and extent of conservation between them to understand the evolutionary dynamics of MERS-CoV.Results
Multiple sequence alignment of the spike (S), membrane (M), enveloped (E) and nucleocapsid (N) proteins was employed to identify the sequence conservation among MERS and Bat (HKU4, HKU5) coronaviruses. We used various in silico tools to predict the conserved antigenic sites. We found that MERS-CoV shared 30 % of its S protein antigenic sites with HKU4 and 70 % with HKU5 bat-CoV. Whereas 100 % of its E, M and N protein’s antigenic sites are found to be conserved with those in HKU4 and HKU5.Conclusion
This sharing suggests that in case of pathogenicity MERS-CoV is more closely related to HKU5 bat-CoV than HKU4 bat-CoV. The conserved epitopes indicates their evolutionary relationship and ancestry of pathogenicity.15.
Jiandong Shi Jing Zhang Sijin Li Jing Sun Yumei Teng Meini Wu Jianfan Li Yanhan Li Ningzhu Hu Haixuan Wang Yunzhang Hu 《PloS one》2015,10(12)
Middle East respiratory syndrome coronavirus (MERS-CoV) with pandemic potential is a major worldwide threat to public health. However, vaccine development for this pathogen lags behind as immunity associated with protection is currently largely unknown. In this study, an immunoinformatics-driven genome-wide screening strategy of vaccine targets was performed to thoroughly screen the vital and effective dominant immunogens against MERS-CoV. Conservancy and population coverage analysis of the epitopes were done by the Immune Epitope Database. The results showed that the nucleocapsid (N) protein of MERS-CoV might be a better protective immunogen with high conservancy and potential eliciting both neutralizing antibodies and T-cell responses compared with spike (S) protein. Further, the B-cell, helper T-cell and cytotoxic T lymphocyte (CTL) epitopes were screened and mapped to the N protein. A total of 15 linear and 10 conformal B-cell epitopes that may induce protective neutralizing antibodies were obtained. Additionally, a total of 71 peptides with 9-mer core sequence were identified as helper T-cell epitopes, and 34 peptides were identified as CTL epitopes. Based on the maximum HLA binding alleles, top 10 helper T-cell epitopes and CTL epitopes that may elicit protective cellular immune responses against MERS-CoV were selected as MERS vaccine candidates. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover the vast majority of the population in 15 geographic regions considered where vaccine would be employed. The B- and T-cell stimulation potentials of the screened epitopes is to be further validated for their efficient use as vaccines against MERS-CoV. Collectively, this study provides novel vaccine target candidates and may prompt further development of vaccines against MERS-CoV and other emerging infectious diseases. 相似文献
16.
17.
18.
Yaoqing Chen Kanagalaghatta R. Rajashankar Yang Yang Sudhakar S. Agnihothram Chang Liu Yi-Lun Lin Ralph S. Baric Fang Li 《Journal of virology》2013,87(19):10777-10783
The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 77 people, with a fatality rate of more than 50%. Alarmingly, the virus demonstrates the capability of human-to-human transmission, raising the possibility of global spread and endangering world health and economy. Here we have identified the receptor-binding domain (RBD) from the MERS-CoV spike protein and determined its crystal structure. This study also presents a structural comparison of MERS-CoV RBD with other coronavirus RBDs, successfully positioning MERS-CoV on the landscape of coronavirus evolution and providing insights into receptor binding by MERS-CoV. Furthermore, we found that MERS-CoV RBD functions as an effective entry inhibitor of MERS-CoV. The identified MERS-CoV RBD may also serve as a potential candidate for MERS-CoV subunit vaccines. Overall, this study enhances our understanding of the evolution of coronavirus RBDs, provides insights into receptor recognition by MERS-CoV, and may help control the transmission of MERS-CoV in humans. 相似文献
19.
Uzma Faridi 《Saudi Journal of Biological Sciences》2018,25(7):1402-1405
Middle East respiratory syndrome is the acute respiratory syndrome caused by betacoronavirus MERS-CoV. The first case of this disease was reported from Saudi Arabia in 2012. This virus is lethal and is a close relative of a severe acute respiratory syndrome (SARS), which is responsible for more than 3000 deaths in 2002–2003. According to Ministry of Health, Saudi Arabia. The number of new cases is 457 in 2015. Riyadh has the highest number of reports in comparison to the other cities. According to this report, males are more susceptible than female, especially after the age of 40. Because of the awareness and early diagnosis the incidence is falling gradually. The pre-existence of another disease like cancer or diabetic etc. boosts the infection. MERS is a zoonotic disease and human to human transmission is low. The MERS-CoV is a RNA virus with protein envelope. On the outer surface, virus has spike like glycoprotein which is responsible for the attachment and entrance inside host cells. There is no specific treatment for the MERS-CoV till now, but drugs are in pipeline which bind with the spike glycoprotein and inhibit its entrance host cells. MERS-CoV and SAR-CoV are from the same genus, so it was thought that the drugs which inhibit the growth of SARS-CoV can also inhibit the growth of MERS-CoV but those drugs are not completely inhibiting virus activity. Until we don’t have proper structure and the treatment of MERS-CoV, We should take precautions, especially the health care workers, Camel owners and Pilgrims during Hajj and Umrah, because they are at a higher risk of getting infected. 相似文献
20.
Ana Moreno Davide Lelli Luca de Sabato Guendalina Zaccaria Arianna Boni Enrica Sozzi Alice Prosperi Antonio Lavazza Eleonora Cella Maria Rita Castrucci Massimo Ciccozzi Gabriele Vaccari 《Virology journal》2017,14(1):239