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https://read.qxmd.com/read/30781790/interferon-regulatory-factor-3-mediated-signaling-limits-middle-east-respiratory-syndrome-mers-coronavirus-propagation-in-cells-from-an-insectivorous-bat
#1
Arinjay Banerjee, Darryl Falzarano, Noreen Rapin, Jocelyne Lew, Vikram Misra
Insectivorous bats are speculated to be ancestral hosts of Middle-East respiratory syndrome (MERS) coronavirus (CoV). MERS-CoV causes disease in humans with thirty-five percent fatality, and has evolved proteins that counteract human antiviral responses. Since bats experimentally infected with MERS-CoV do not develop signs of disease, we tested the hypothesis that MERS-CoV would replicate less efficiently in bat cells than in human cells because of its inability to subvert antiviral responses in bat cells. We infected human and bat ( Eptesicus fuscus ) cells with MERS-CoV and observed that the virus grew to higher titers in human cells...
February 13, 2019: Viruses
https://read.qxmd.com/read/30775355/absence-of-neutralizing-activity-in-serum-1-year-after-successful-treatment-with-antivirals-and-recovery-from-mers-in-south-korea
#2
Jun Yong Choi, Jin Ok Oh, Jin Young Ahn, Heun Choi, Jung Ho Kim, Hye Seong, Su Jin Jeong, Nam Su Ku, Joon-Sup Yeom, Jae-Phil Choi
We evaluated the neutralizing activity in serum from three patients >1 year after recovery from Middle East respiratory syndrome (MERS) associated with mild pneumonia treated with antivirals during the MERS outbreak in South Korea at 2015. The neutralizing activity in serum was measured by pseudovirus inhibition assays. Three-fold diluted serum of subjects showed only 9.7%, 10.3%, and 2.2% reductions in relative light units. So, significant neutralizing activity was not demonstrated in any sera of three patients with mild pneumonia >1 year after being successfully treated with antiviral agents and recovering from MERS coronavirus infection...
January 2019: Clinical and Experimental Vaccine Research
https://read.qxmd.com/read/30753126/genetic-characterization-of-middle-east-respiratory-syndrome-coronavirus-south-korea-2018
#3
Yoon-Seok Chung, Jeong Min Kim, Heui Man Kim, Kye Ryeong Park, Anna Lee, Nam-Joo Lee, Mi-Seon Kim, Jun Sub Kim, Chi-Kyeong Kim, Jae In Lee, Chun Kang
We evaluated genetic variation in Middle East respiratory syndrome coronavirus (MERS-CoV) imported to South Korea in 2018 using specimens from a patient and isolates from infected Caco-2 cells. The MERS-CoV strain in this study was genetically similar to a strain isolated in Riyadh, Saudi Arabia, in 2017.
May 17, 2019: Emerging Infectious Diseases
https://read.qxmd.com/read/30744201/potential-intermediate-hosts-for-coronavirus-transmission-no-evidence-of-clade-2c-coronaviruses-in-domestic-livestock-from-ghana
#4
Philip El-Duah, Augustina Sylverken, Michael Owusu, Richmond Yeboah, Jones Lamptey, Yaw Oppong Frimpong, Vitus Burimuah, Christopher Antwi, Raphael Folitse, Olivia Agbenyega, Samuel Oppong, Yaw Adu-Sarkodie
The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV), nearly a decade ago with worldwide distribution, was believed to be of zoonotic origin from bats with dromedary camels as intermediate hosts. There is a likelihood of other domestic livestock serving as intermediate hosts for this virus. The presence of coronaviruses, closely related to MERS-CoV in Ghanaian bats, presented the opportunity to test the hypothesis of transmissibility of this virus through domestic livestock species. The possible interactions between livestock and bats in 31 household farms were accessed by observation and interviews with farmers...
February 10, 2019: Tropical Medicine and Infectious Disease
https://read.qxmd.com/read/30717685/a-case-crossover-analysis-of-the-impact-of-weather-on-primary-cases-of-middle-east-respiratory-syndrome
#5
Emma G Gardner, David Kelton, Zvonimir Poljak, Maria Van Kerkhove, Sophie von Dobschuetz, Amy L Greer
BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic in dromedary camels in the Arabian Peninsula, and zoonotic transmission to people is a sporadic event. In the absence of epidemiological data on the reservoir species, patterns of zoonotic transmission have largely been approximated from primary human cases. This study aimed to identify meteorological factors that may increase the risk of primary MERS infections in humans. METHODS: A case-crossover design was used to identify associations between primary MERS cases and preceding weather conditions within the 2-week incubation period in Saudi Arabia using univariable conditional logistic regression...
February 4, 2019: BMC Infectious Diseases
https://read.qxmd.com/read/30712865/unexpected-receptor-functional-mimicry-elucidates-activation-of-coronavirus-fusion
#6
Alexandra C Walls, Xiaoli Xiong, Young-Jun Park, M Alejandra Tortorici, Joost Snijder, Joel Quispe, Elisabetta Cameroni, Robin Gopal, Mian Dai, Antonio Lanzavecchia, Maria Zambon, Félix A Rey, Davide Corti, David Veesler
Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses. The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies. To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors...
January 23, 2019: Cell
https://read.qxmd.com/read/30690213/macrolides-in-critically-ill-patients-with-middle-east-respiratory-syndrome
#7
Yaseen M Arabi, Ahmad M Deeb, Fahad Al-Hameed, Yasser Mandourah, Ghaleb A Almekhlafi, Anees A Sindi, Awad Al-Omari, Sarah Shalhoub, Ahmed Mady, Basem Alraddadi, Abdullah Almotairi, Kasim Al Khatib, Ahmed Abdulmomen, Ismael Qushmaq, Othman Solaiman, Abdulsalam M Al-Aithan, Rajaa Al-Raddadi, Ahmad Ragab, Abdulrahman Al Harthy, Ayman Kharaba, Jesna Jose, Tarek Dabbagh, Robert A Fowler, Hanan H Balkhy, Laura Merson, Frederick G Hayden
OBJECTIVES: Macrolides have been reported to be associated with improved outcomes in patients with viral pneumonia related to influenza and other viruses, possibly because of their immune-modulatory effects. Macrolides have frequently been used in patients with Middle East Respiratory Syndrome (MERS). This study investigated the association of macrolides with 90-day mortality and MERS coronavirus (CoV) RNA clearance in critically ill patients with MERS. METHODS: This retrospective analysis of a multicenter cohort database included 14 tertiary-care hospitals in five cities in Saudi Arabia...
January 25, 2019: International Journal of Infectious Diseases: IJID
https://read.qxmd.com/read/30688313/a-fluorogenic-peptide-cleavage-assay-to-screen-for-proteolytic-activity-applications-for-coronavirus-spike-protein-activation
#8
Javier A Jaimes, Jean K Millet, Monty E Goldstein, Gary R Whittaker, Marco R Straus
Enveloped viruses such as coronaviruses or influenza virus require proteolytic cleavage of their fusion protein to be able to infect the host cell. Often viruses exhibit cell and tissue tropism and are adapted to specific cell or tissue proteases. Moreover, these viruses can introduce mutations or insertions into their genome during replication that may affect the cleavage, and thus can contribute to adaptations to a new host. Here, we present a fluorogenic peptide cleavage assay that allows a rapid screening of peptides mimicking the cleavage site of viral fusion proteins...
January 9, 2019: Journal of Visualized Experiments: JoVE
https://read.qxmd.com/read/30683171/bovine-like-coronaviruses-in-domestic-and-wild-ruminants
#9
Haitham Mohamed Amer
Coronaviruses (CoVs) produce a wide spectrum of disease syndromes in different mammalian and avian host species. These viruses are well-recognized for their ability to change tissue tropism, to hurdle the interspecies barriers and to adapt ecological variations. It is predicted that the inherent genetic diversity of CoVs caused by accumulation of point mutations and high frequency of homologous recombination is the principal determinant of these competences. Several CoVs (e.g. Severe acute respiratory syndrome-CoV, Middle East respiratory syndrome-CoV) have been recorded to cross the interspecies barrier, inducing different disease conditions in variable animal hosts...
December 2018: Animal Health Research Reviews
https://read.qxmd.com/read/30676269/what-have-we-learned-about-middle-east-respiratory-syndrome-coronavirus-emergence-in-humans-a-systematic-literature-review
#10
Patrick Dawson, Mamunur Rahman Malik, Faruque Parvez, Stephen S Morse
BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in humans in 2012. A systematic literature review was conducted to synthesize current knowledge and identify critical knowledge gaps. MATERIALS AND METHODS: We conducted a systematic review on MERS-CoV using PRISMA guidelines. We identified 407 relevant, peer-reviewed publications and selected 208 of these based on their contributions to four key areas: virology; clinical characteristics, outcomes, therapeutic and preventive options; epidemiology and transmission; and animal interface and the search for natural hosts of MERS-CoV...
January 24, 2019: Vector Borne and Zoonotic Diseases
https://read.qxmd.com/read/30658390/middle-east-respiratory-syndrome-vaccine-candidates-cautious-optimism
#11
REVIEW
Craig Schindewolf, Vineet D Menachery
Efforts towards developing a vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV) have yielded promising results. Utilizing a variety of platforms, several vaccine approaches have shown efficacy in animal models and begun to enter clinical trials. In this review, we summarize the current progress towards a MERS-CoV vaccine and highlight potential roadblocks identified from previous attempts to generate coronavirus vaccines.
January 17, 2019: Viruses
https://read.qxmd.com/read/30654597/characterization-of-the-lipidomic-profile-of-human-coronavirus-infected-cells-implications-for-lipid-metabolism-remodeling-upon-coronavirus-replication
#12
Bingpeng Yan, Hin Chu, Dong Yang, Kong-Hung Sze, Pok-Man Lai, Shuofeng Yuan, Huiping Shuai, Yixin Wang, Richard Yi-Tsun Kao, Jasper Fuk-Woo Chan, Kwok-Yung Yuen
Lipids play numerous indispensable cellular functions and are involved in multiple steps in the replication cycle of viruses. Infections by human-pathogenic coronaviruses result in diverse clinical outcomes, ranging from self-limiting flu-like symptoms to severe pneumonia with extrapulmonary manifestations. Understanding how cellular lipids may modulate the pathogenicity of human-pathogenic coronaviruses remains poor. To this end, we utilized the human coronavirus 229E (HCoV-229E) as a model coronavirus to comprehensively characterize the host cell lipid response upon coronavirus infection with an ultra-high performance liquid chromatography-mass spectrometry (UPLC⁻MS)-based lipidomics approach...
January 16, 2019: Viruses
https://read.qxmd.com/read/30646569/advances-in-mers-cov-vaccines-and-therapeutics-based-on-the-receptor-binding-domain
#13
REVIEW
Yusen Zhou, Yang Yang, Jingwei Huang, Shibo Jiang, Lanying Du
Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is an infectious virus that was first reported in 2012. The MERS-CoV genome encodes four major structural proteins, among which the spike (S) protein has a key role in viral infection and pathogenesis. The receptor-binding domain (RBD) of the S protein contains a critical neutralizing domain and is an important target for development of MERS vaccines and therapeutics. In this review, we describe the relevant features of the MERS-CoV S-protein RBD, summarize recent advances in the development of MERS-CoV RBD-based vaccines and therapeutic antibodies, and illustrate potential challenges and strategies to further improve their efficacy...
January 14, 2019: Viruses
https://read.qxmd.com/read/30646565/from-sars-to-mers-thrusting-coronaviruses-into-the-spotlight
#14
REVIEW
Zhiqi Song, Yanfeng Xu, Linlin Bao, Ling Zhang, Pin Yu, Yajin Qu, Hua Zhu, Wenjie Zhao, Yunlin Han, Chuan Qin
Coronaviruses (CoVs) have formerly been regarded as relatively harmless respiratory pathogens to humans. However, two outbreaks of severe respiratory tract infection, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), as a result of zoonotic CoVs crossing the species barrier, caused high pathogenicity and mortality rates in human populations. This brought CoVs global attention and highlighted the importance of controlling infectious pathogens at international borders...
January 14, 2019: Viruses
https://read.qxmd.com/read/30646495/potent-mers-cov-fusion-inhibitory-peptides-identified-from-hr2-domain-in-spike-protein-of-bat-coronavirus-hku4
#15
Shuai Xia, Qiaoshuai Lan, Jing Pu, Cong Wang, Zezhong Liu, Wei Xu, Qian Wang, Huan Liu, Shibo Jiang, Lu Lu
The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and caused continual outbreaks worldwide with high mortality. However, no effective anti-MERS-CoV drug is currently available. Recently, numerous evolutionary studies have suggested that MERS-CoV originated from bat coronavirus (BatCoV). We herein reported that three peptides derived from the HR2 region in spike protein of BatCoV HKU4, including HKU4-HR2P1, HKU4-HR2P2 and HKU4-HR2P3, could bind the MERS-CoV HR1-derived peptide to form a six-helix bundle (6-HB) with high stability...
January 14, 2019: Viruses
https://read.qxmd.com/read/30644840/structure-and-oligomerization-state-of-the-c-terminal-region-of-the-middle-east-respiratory-syndrome-coronavirus-nucleoprotein
#16
Thi Hong Van Nguyen, Julie Lichière, Bruno Canard, Nicolas Papageorgiou, Sarah Attoumani, François Ferron, Bruno Coutard
Middle East respiratory syndrome coronavirus (MERS-CoV) is a human pathogen responsible for a severe respiratory illness that emerged in 2012. Structural information about the proteins that constitute the viral particle is scarce. In order to contribute to a better understanding of the nucleoprotein (N) in charge of RNA genome encapsidation, the structure of the C-terminal domain of N from MERS-CoV obtained using single-crystal X-ray diffraction is reported here at 1.97 Å resolution. The molecule is present as a dimer in the crystal structure and this oligomerization state is confirmed in solution, as measured by additional methods including small-angle X-ray scattering measurements...
January 1, 2019: Acta Crystallographica. Section D, Structural Biology
https://read.qxmd.com/read/30634407/complement-receptor-c5ar1-inhibition-reduces-pyroptosis-in-hdpp4-transgenic-mice-infected-with-mers-cov
#17
Yuting Jiang, Junfeng Li, Yue Teng, Hong Sun, Guang Tian, Lei He, Pei Li, Yuehong Chen, Yan Guo, Jiangfan Li, Guangyu Zhao, Yusen Zhou, Shihui Sun
Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages...
January 9, 2019: Viruses
https://read.qxmd.com/read/30634396/bats-and-coronaviruses
#18
REVIEW
Arinjay Banerjee, Kirsten Kulcsar, Vikram Misra, Matthew Frieman, Karen Mossman
Bats are speculated to be reservoirs of several emerging viruses including coronaviruses (CoVs) that cause serious disease in humans and agricultural animals. These include CoVs that cause severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), porcine epidemic diarrhea (PED) and severe acute diarrhea syndrome (SADS). Bats that are naturally infected or experimentally infected do not demonstrate clinical signs of disease. These observations have allowed researchers to speculate that bats are the likely reservoirs or ancestral hosts for several CoVs...
January 9, 2019: Viruses
https://read.qxmd.com/read/30631056/srebp-dependent-lipidomic-reprogramming-as-a-broad-spectrum-antiviral-target
#19
Shuofeng Yuan, Hin Chu, Jasper Fuk-Woo Chan, Zi-Wei Ye, Lei Wen, Bingpeng Yan, Pok-Man Lai, Kah-Meng Tee, Jingjing Huang, Dongdong Chen, Cun Li, Xiaoyu Zhao, Dong Yang, Man Chun Chiu, Cyril Yip, Vincent Kwok-Man Poon, Chris Chung-Sing Chan, Kong-Hung Sze, Jie Zhou, Ivy Hau-Yee Chan, Kin-Hang Kok, Kelvin Kai-Wang To, Richard Yi-Tsun Kao, Johnson Yiu-Nam Lau, Dong-Yan Jin, Stanley Perlman, Kwok-Yung Yuen
Viruses are obligate intracellular microbes that exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. Here, by exploring a lipid library, we show that AM580, a retinoid derivative and RAR-α agonist, is highly potent in interrupting the life cycle of diverse viruses including Middle East respiratory syndrome coronavirus and influenza A virus. Using click chemistry, the overexpressed sterol regulatory element binding protein (SREBP) is shown to interact with AM580, which accounts for its broad-spectrum antiviral activity...
January 10, 2019: Nature Communications
https://read.qxmd.com/read/30626688/tmprss2-contributes-to-virus-spread-and-immunopathology-in-the-airways-of-murine-models-after-coronavirus-infection
#20
Naoko Iwata-Yoshikawa, Tadashi Okamura, Yukiko Shimizu, Hideki Hasegawa, Makoto Takeda, Noriyo Nagata
Transmembrane serine protease TMPRSS2 activates the spike protein of highly pathogenic human coronaviruses such as severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV). In vitro , activation induces virus-cell membrane fusion at the cell surface. However, the roles of TMPRSS2 during coronavirus infection in vivo are unclear. Here, we used animal models of SARS-CoV and MERS-CoV infection to investigate the role of TMPRSS2. Th-1-prone C57BL/6 mice and TMPRSS2-knockout (KO) mice were used for SARS-CoV infection, and transgenic mice expressing the human MERS-CoV receptor, hDPP4-Tg mice, and TMPRSS2-KO hDPP4-Tg mice were used for MERS-CoV infection...
January 9, 2019: Journal of Virology
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