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https://www.readbyqxmd.com/read/30110630/adaptive-evolution-of-mers-cov-to-species-variation-in-dpp4
#1
Michael Letko, Kerri Miazgowicz, Rebekah McMinn, Stephanie N Seifert, Isabel Sola, Luis Enjuanes, Aaron Carmody, Neeltje van Doremalen, Vincent Munster
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. Variation in the host receptor, dipeptidyl peptidase 4 (DPP4), can block the interaction with the MERS-CoV spike protein and form a species barrier to infection. To better understand the species adaptability of MERS-CoV, we identified a suboptimal species-derived variant of DPP4 to study viral adaption...
August 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/30107872/lack-of-serological-evidence-of-middle-east-respiratory-syndrome-coronavirus-infection-in-virus-exposed-camel-abattoir-workers-in-nigeria-2016
#2
Ray Ty So, Ranawaka Apm Perera, Jamiu O Oladipo, Daniel Kw Chu, Sulyman A Kuranga, Kin-Ho Chan, Eric Hy Lau, Samuel Ms Cheng, Leo Lm Poon, Richard J Webby, Malik Peiris
BackgroundMiddle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic threat of global public health concern and dromedary camels are the source of zoonotic infection. Although MERS-CoV is enzootic in dromedaries in Africa as well as the Middle East, zoonotic disease has not been reported in Africa. Methods : In an abattoir in Kano, Nigeria, we tested nasal swabs from camels and investigated 261 humans with repeated occupational exposure to camels, many of whom also reported drinking fresh camel milk (n = 138) or urine (n = 94) or using camel urine for medicinal purposes (n = 96)...
August 2018: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/30104551/reported-direct-and-indirect-contact-with-dromedary-camels-among-laboratory-confirmed-mers-cov-cases
#3
Romy Conzade, Rebecca Grant, Mamunur Rahman Malik, Amgad Elkholy, Mohamed Elhakim, Dalia Samhouri, Peter K Ben Embarek, Maria D Van Kerkhove
Dromedary camels ( Camelus dromedarius ) are now known to be the vertebrate animal reservoir that intermittently transmits the Middle East respiratory syndrome coronavirus (MERS-CoV) to humans. Yet, details as to the specific mechanism(s) of zoonotic transmission from dromedaries to humans remain unclear. The aim of this study was to describe direct and indirect contact with dromedaries among all cases, and then separately for primary, non-primary, and unclassified cases of laboratory-confirmed MERS-CoV reported to the World Health Organization (WHO) between 1 January 2015 and 13 April 2018...
August 13, 2018: Viruses
https://www.readbyqxmd.com/read/30103157/arch-shaped-multiple-target-sensing-for-rapid-diagnosis-and-identification-of-emerging-infectious-pathogens
#4
Bonhan Koo, Ki Ho Hong, Choong Eun Jin, Ji Yeun Kim, Sung-Han Kim, Yong Shin
Rapid identification of emerging infectious pathogens is crucial for preventing public health threats. Various pathogen detection techniques have been introduced; however, most techniques are time-consuming and lack multiple-target detection specificity. Although multiple-target detection techniques can distinguish emerging infectious pathogens from related pathogens, direct amplification methods have not been widely examined. Here, we present a novel arch-shaped multiple-target sensor capable of rapid pathogen identification using direct amplification in clinical samples...
August 8, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/30102495/mortality-rate-of-icu-patients-with-the-middle-east-respiratory-syndrome-coronavirus-infection-at-king-fahad-hospital-jeddah-saudi-arabia
#5
Mohammed A Garout, Hani A A Jokhdar, Imad A Aljahdali, Ahmed R Zein, Reda A Goweda, Abdurahman Hassan-Hussein
OBJECTIVE: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a novel coronavirus circulating in the Arabian Peninsula since September 2012. It leads to significant respiratory disease and among patients with co-morbidities is associated with high mortality. This research studied the mortality rate of MERS-CoV among intensive care unit (ICU) patients and the correlation of mortality with different co-morbidities. METHODS: This was a retrospective observational study conducted at the Intensive Care Unit of the King Fahad Hospital, Jeddah, Saudi Arabia...
June 2018: Central European Journal of Public Health
https://www.readbyqxmd.com/read/30101189/chimeric-camel-human-heavy-chain-antibodies-protect-against-mers-cov-infection
#6
V Stalin Raj, Nisreen M A Okba, Javier Gutierrez-Alvarez, Dubravka Drabek, Brenda van Dieren, W Widagdo, Mart M Lamers, Ivy Widjaja, Raul Fernandez-Delgado, Isabel Sola, Albert Bensaid, Marion P Koopmans, Joaquim Segalés, Albert D M E Osterhaus, Berend Jan Bosch, Luis Enjuanes, Bart L Haagmans
Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause outbreaks in humans as a result of spillover events from dromedaries. In contrast to humans, MERS-CoV-exposed dromedaries develop only very mild infections and exceptionally potent virus-neutralizing antibody responses. These strong antibody responses may be caused by affinity maturation as a result of repeated exposure to the virus or by the fact that dromedaries-apart from conventional antibodies-have relatively unique, heavy chain-only antibodies (HCAbs)...
August 2018: Science Advances
https://www.readbyqxmd.com/read/30089512/human-%C3%AE-defensin-2-plays-a-regulatory-role-in-innate-antiviral-immunity-and-is-capable-of-potentiating-the-induction-of-antigen-specific-immunity
#7
Ju Kim, Ye Lin Yang, Sun-Hee Jang, Yong-Suk Jang
BACKGROUND: Antimicrobial peptides (AMPs) are primarily known for their innate immune defense against invading microorganisms, including viruses. In addition, recent research has suggested their modulatory activity in immune induction. Given that most subunit vaccines require an adjuvant to achieve effective immune induction through the activation of innate immunity, AMPs are plausible candidate molecules for stimulating not only innate immune but also adaptive immune responses. RESULTS: In this study, we investigated the ability of human β-defensin (HBD) 2 to promote antiviral immunity in vitro and in vivo using a receptor-binding domain (RBD) of Middle East respiratory syndrome-coronavirus (MERS-CoV) spike protein (S RBD) as a model antigen (Ag)...
August 8, 2018: Virology Journal
https://www.readbyqxmd.com/read/30060038/immune-responses-to-mers-coronavirus-during-the-acute-and-convalescent-phases-of-human-infection
#8
Hyoung-Shik Shin, Yeonjae Kim, Gayeon Kim, Ji Yeon Lee, Ina Jeong, Joon-Sung Joh, Hana Kim, Eunjin Chang, Soo Yeon Sim, Jun-Sun Park, Dong-Gyun Lim
Background: An understanding of immune responses against the Middle East respiratory syndrome (MERS) is important for the development of treatments and preventive measures. Here, we investigated the spectrum of immune responses occurring in patients with MERS during the early period of infection. Methods: We obtained peripheral blood samples from 27 hospitalized patients recruited during the epidemic that occurred in 2015 in South Korea. Plasma cytokines/chemokines and antibodies were quantified...
July 27, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/30058403/prospects-for-a-mers-cov-spike-vaccine
#9
Yusen Zhou, Shibo Jiang, Lanying Du
Six years have passed since Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV), a newly emerging infectious virus, was first reported in 2012. Although MERS-CoV has had a consistently high mortality rate in humans, no vaccines have been approved to prevent MERS-CoV infection in humans. MERS-CoV spike (S) protein is a key target for development of MERS vaccines. Areas covered: In this review, we illustrate the structure and function of S protein as a vaccine target, describe available animal models for evaluating MERS vaccines, and summarize recent progress on MERS-CoV S-based vaccines, focusing on their ability to elicit antibody and/or cellular immune responses, neutralizing antibodies, and protection against MERS-CoV infection in different models...
August 9, 2018: Expert Review of Vaccines
https://www.readbyqxmd.com/read/30021905/middle-east-respiratory-syndrome-coronavirus-spike-protein-is-not-activated-directly-by-cellular-furin-during-viral-entry-into-target-cells
#10
Shutoku Matsuyama, Kazuya Shirato, Miyuki Kawase, Yutaka Terada, Kengo Kawachi, Shuetsu Fukushi, Wataru Kamitani
Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes host cellular proteases to enter cells. A previous report shows that furin, which is distributed mainly in the Golgi apparatus and cycled to the cell surface and endosomes, proteolytically activates the MERS-CoV spike (S) protein following receptor binding to mediate fusion between the viral and cellular membranes. Here, we re-examined furin usage by MERS-CoV using a real-time PCR-based virus cell entry assay after inhibition of cellular proteases...
July 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/30016543/proficiency-testing-for-the-detection-of-middle-east-respiratory-syndrome-coronavirus-demonstrates-global-capacity-to-detect-mers-cov
#11
T Theis, K A Lau, J L Gray, C J Oxenford, G J Walker, W D Rawlinson
The first reported case of Middle East respiratory syndrome-coronavirus (MERS-CoV) infection was identified in Saudi Arabia in September 2012, since which time there have been over 2,000 laboratory-confirmed cases, including 750 deaths in 27 countries. Nucleic acid testing (NAT) is the preferred method for the detection of MERS-CoV. A single round of a Proficiency Testing Program (PTP) was used to assess the capability of laboratories globally to accurately detect the presence of MERS-CoV using NAT. A panel of eleven lyophilized specimens containing different viral loads of MERS-CoV, common coronaviruses, and in vitro RNA transcripts was distributed to laboratories in all six WHO Regions...
July 17, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/30013082/a-spike-modified-middle-east-respiratory-syndrome-coronavirus-mers-cov-infectious-clone-elicits-mild-respiratory-disease-in-infected-rhesus-macaques
#12
Adam S Cockrell, Joshua C Johnson, Ian N Moore, David X Liu, Kevin W Bock, Madeline G Douglas, Rachel L Graham, Jeffrey Solomon, Lisa Torzewski, Christopher Bartos, Randy Hart, Ralph S Baric, Reed F Johnson
The recurrence of new human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) underscores the need for effective therapeutic countermeasures. Nonhuman primate models are considered the gold standard for preclinical evaluation of therapeutic countermeasures. However, MERS-CoV-induced severe respiratory disease in humans is associated with high viral loads in the lower respiratory tract, which may be difficult to achieve in nonhuman primate models. Considering this limitation, we wanted to ascertain the effectiveness of using a MERS-CoV infectious clone (icMERS-0) previously shown to replicate to higher titers than the wild-type EMC 2012 strain...
July 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30012113/clinical-management-of-respiratory-syndrome-in-patients-hospitalized-for-suspected-middle-east-respiratory-syndrome-coronavirus-infection-in-the-paris-area-from-2013-to-2016
#13
A Bleibtreu, S Jaureguiberry, N Houhou, D Boutolleau, H Guillot, D Vallois, J C Lucet, J Robert, B Mourvillier, J Delemazure, M Jaspard, F X Lescure, C Rioux, E Caumes, Y Yazdanapanah
BACKGROUND: Patients with suspected Middle East respiratory syndrome coronavirus (MERS-CoV) infection should be hospitalized in isolation wards to avoid transmission. This suspicion can also lead to medical confusion and inappropriate management of acute respiratory syndrome due to causes other than MERS-CoV. METHODS: We studied the characteristics and outcome of patients hospitalized for suspected MERS-CoV infection in the isolation wards of two referral infectious disease departments in the Paris area between January 2013 and December 2016...
July 16, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29996104/structural-definition-of-a-unique-neutralization-epitope-on-the-receptor-binding-domain-of-mers-cov-spike-glycoprotein
#14
Senyan Zhang, Panpan Zhou, Pengfei Wang, Yangyang Li, Liwei Jiang, Wenxu Jia, Han Wang, Angela Fan, Dongli Wang, Xuanling Shi, Xianyang Fang, Michal Hammel, Shuying Wang, Xinquan Wang, Linqi Zhang
The major mechanism of antibody-mediated neutralization of the Middle East respiratory syndrome coronavirus (MERS-CoV) involves competition with the cellular receptor dipeptidyl peptidase 4 (DPP4) for binding to the receptor-binding domain (RBD) of the spike (S) glycoprotein. Here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody MERS-4. Structurally, MERS-4 approached the RBD from the outside of the RBD-DPP4 binding interface. Such binding resulted in the folding of the β5-β6 loop toward a shallow groove on the RBD interface critical for accommodating DPP4...
July 10, 2018: Cell Reports
https://www.readbyqxmd.com/read/29976755/tmprss11a-activates-the-influenza-a-virus-hemagglutinin-and-the-mers-coronavirus-spike-protein-and-is-insensitive-against-blockade-by-hai-1
#15
Pawel Zmora, Markus Hoffmann, Heike Kollmus, Anna-Sophie Moldenhauer, Olga Danov, Armin Braun, Michael Winkler, Klaus Schughart, Stefan Pöhlmann
The influenza virus hemagglutinin (HA) facilitates viral entry into target cells. Cleavage of HA by host cell proteases is essential for viral infectivity and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease (TTSP) TMPRSS2 has been identified as an HA activator in cell culture and in the infected host. However, it is less clear whether TMPRSS2-related enzymes can also activate HA for spread in target cells. Moreover, the activity of cellular serine protease inhibitors against HA-activating TTSPs is poorly understood...
July 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29956635/lead-molecule-prediction-and-characterization-for-designing-mers-cov-3c-like-protease-inhibitors-an-in-silico-approach
#16
Md Mostafijur Rahman, Md Bayejid Hosen, M Zakir Hossain Howlader, Yearul Kabir
BACKGROUND: 3C-like protease also called the main protease is an essential enzyme for the completion of the life cycle of Middle East Respiratory Syndrome Coronavirus. In our study we predicted compounds which are capable of inhibiting 3C-like protease,and thus inhibit the lifecycle of Middle East Respiratory Syndrome Coronavirus using in silico methods. METHODS: Lead like compounds and drug molecules which are capable of inhibiting 3C-like protease was identified by structure-based virtual screening and ligand-based virtual screening method...
June 29, 2018: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/29950581/experimental-infection-of-dromedaries-with-middle-east-respiratory-syndrome-coronavirus-is-accompanied-by-massive-ciliary-loss-and-depletion-of-the-cell-surface-receptor-dipeptidyl-peptidase-4
#17
Ann-Kathrin Haverkamp, Annika Lehmbecker, Ingo Spitzbarth, Widagdo Widagdo, Bart L Haagmans, Joaquim Segalés, Julia Vergara-Alert, Albert Bensaid, Judith M A van den Brand, Albert D M E Osterhaus, Wolfgang Baumgärtner
Middle East respiratory syndrome (MERS) represents an important respiratory disease accompanied by lethal outcome in one-third of human patients. Recent data indicate that dromedaries represent an important source of infection, although information regarding viral cell tropism and pathogenesis is sparse. In the current study, tissues of eight dromedaries receiving inoculation of MERS-Coronavirus (MERS-CoV) after recombinant Modified-Vaccinia-Virus-Ankara (MVA-S)-vaccination (n = 4), MVA-vaccination (mock vaccination, n = 2) and PBS application (mock vaccination, n = 2), respectively, were investigated...
June 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29950512/estimating-the-distance-to-an-epidemic-threshold
#18
Eamon B O'Dea, Andrew W Park, John M Drake
The epidemic threshold of the susceptible-infected-recovered model is a boundary separating parameters that permit epidemics from those that do not. This threshold corresponds to parameters where the system's equilibrium becomes unstable. Consequently, we use the average rate at which deviations from the equilibrium shrink to define a distance to this threshold. However, the vital dynamics of the host population may occur slowly even when transmission is far from threshold levels. Here, we show analytically how such slow dynamics can prevent estimation of the distance to the threshold from fluctuations in the susceptible population...
June 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29950421/a-novel-nanobody-targeting-middle-east-respiratory-syndrome-coronavirus-mers-cov-receptor-binding-domain-has-potent-cross-neutralizing-activity-and-protective-efficacy-against-mers-cov
#19
Guangyu Zhao, Lei He, Shihui Sun, Hongjie Qiu, Wanbo Tai, Jiawei Chen, Jiangfan Li, Yuehong Chen, Yan Guo, Yufei Wang, Jian Shang, Kaiyuan Ji, Ruiwen Fan, Enqi Du, Shibo Jiang, Fang Li, Lanying Du, Yusen Zhou
The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) continues to infect humans and camels, calling for efficient, cost-effective, and broad-spectrum strategies to control its spread. Nanobodies (Nbs) are single-domain antibodies derived from camelids and sharks, and are potentially cost-effective antivirals with small size and great expression yield. In this study, we developed a novel neutralizing Nb (NbMS10) and its human-Fc-fused version (NbMS10-Fc), both of which target the MERS-CoV spike protein receptor-binding domain (RBD)...
June 27, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29949167/global-seasonal-occurrence-of-middle-east-respiratory-syndrome-coronavirus-mers-cov-infection
#20
M S Nassar, M A Bakhrebah, S A Meo, M S Alsuabeyl, W A Zaher
OBJECTIVE: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an evolving global health crisis. Despite recent efforts, there are numerous notable gaps in the understanding of MERS-CoV seasonal diversity. We aimed at investigating the global seasonal occurrence of Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreaks. MATERIALS AND METHODS: We obtained the data on the prevalence and occurrence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection from the World Health Organization (WHO) for all the MERS cases reported from the various countries and their allied ministries...
June 2018: European Review for Medical and Pharmacological Sciences
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