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Jeanne M Sisk, Matthew B Frieman, Carolyn E Machamer
Enveloped viruses gain entry into host cells by fusing with cellular membranes, a step that is required for virus replication. Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and infectious bronchitis virus (IBV), fuse at the plasma membrane or use receptor-mediated endocytosis and fuse with endosomes, depending on the cell or tissue type. The virus spike (S) protein mediates fusion with the host cell membrane. We have shown previously that an Abelson (Abl) kinase inhibitor, imatinib, significantly reduces SARS-CoV and MERS-CoV viral titres and prevents endosomal entry by HIV SARS S and MERS S pseudotyped virions...
March 20, 2018: Journal of General Virology
Anwar E Ahmed, Hamdan Al-Jahdali, Abeer N Alshukairi, Mody Alaqeel, Salma S Siddiq, Hanan A Alsaab, Ezzeldin A Sakr, Hamed A Alyahya, Munzir M Alandonisi, Alaa T Subedar, Nouf M Aloudah, Salim Baharoon, Majid A Alsalamah, Sameera Al Johani, Mohammed G Alghamdi
BACKGROUND: Rapidly and accurately identifying individuals who are at high risk for Middle East respiratory syndrome coronavirus (MERS-CoV) remains a major challenge for the medical and scientific communities. The aim of this study was to develop and validate a risk prediction model for the screening of suspected cases of MERS-CoV infection in patients who had developed pneumonia. METHODS: A two-center retrospective case-control study was done, including 360 patients with confirmed pneumonia who were evaluated for MERS-CoV infection by Real-time reverse-transcription polymerase chain reaction (rRT-PCR) from September 1, 2012 to June 1, 2016 at King Abdulaziz Medical City in Riyadh (KAMC-R) and King Fahd General Hospital in Jeddah (KFGH-JED)...
March 14, 2018: International Journal of Infectious Diseases: IJID
Stephen Gikonyo, Tabitha Kimani, Joseph Matere, Joshua Kimutai, Stella G Kiambi, Austine O Bitek, K J Z Juma Ngeiywa, Yilma J Makonnen, Astrid Tripodi, Subhash Morzaria, Juan Lubroth, Gabriel Rugalema, Folorunso Oludayo Fasina
Dromedary camels have been implicated consistently as the source of Middle East respiratory syndrome coronavirus (MERS-CoV) human infections and attention to prevent and control it has focused on camels. To understanding the epidemiological role of camels in the transmission of MERS-CoV, we utilized an iterative empirical process in Geographic Information System (GIS) to identify and qualify potential hotspots for maintenance and circulation of MERS-CoV, and produced risk-based surveillance sites in Kenya. Data on camel population and distribution were used to develop camel density map, while camel farming system was defined using multi-factorial criteria including the agro-ecological zones (AEZs), production and marketing practices...
March 16, 2018: EcoHealth
Anushka C Galasiti Kankanamalage, Yunjeong Kim, Vishnu C Damalanka, Athri D Rathnayake, Anthony R Fehr, Nurjahan Mehzabeen, Kevin P Battaile, Scott Lovell, Gerald H Lushington, Stanley Perlman, Kyeong-Ok Chang, William C Groutas
There are currently no approved vaccines or small molecule therapeutics available for the prophylaxis or treatment of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infections. MERS-CoV 3CL protease is essential for viral replication; consequently, it is an attractive target that provides a potentially effective means of developing small molecule therapeutics for combatting MERS-CoV. We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties...
March 6, 2018: European Journal of Medicinal Chemistry
Khadega A Abuelgasim, Yousef Alsharhan, Tariq Alenzi, Abdulaziz Alhazzani, Yosra Z Ali, Abdul Rahman Jazieh
BACKGROUND: A significant proportion of cancer patients use complementary and alternative medicine (CAM) along with conventional therapies (CT), whereas a smaller proportion delay or defer CT in favor of CAM. Previous studies exploring CAM use among cancer patients in the Middle East region have shown discrepant results. This study investigates the prevalence and pattern of CAM use by Saudi cancer patients. It also discusses the possible benefits and harm related to CAM use by cancer patients, and it explores the beliefs patients hold and their transparency with health care providers regarding their CAM use...
March 12, 2018: BMC Complementary and Alternative Medicine
Huda F Abbag, Awad Ahmed El-Mekki, Ali Aobaid Ali Al Bshabshe, Ahmed A Mahfouz, Ahasen A Al-Dosry, Rasha T Mirdad, Nora F AlKhttabi, Lubna F Abbag
INTRODUCTION: Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the family Coronaviridae, and is named for the crown-like spikes on its surface. The clinical presentation of MERS-CoV infection ranges from asymptomatic to very severe disease, and the classical presentation includes fever, cough chills, sore throat, myalgia, and arthralgia. METHODS: A cross-sectional study of 339 healthcare personnel was conducted over an 8-month period in the Aseer region of Saudi Arabia using a structured survey that included demographic information and questions testing participant's knowledge...
March 7, 2018: Journal of Infection and Public Health
Lingshu Wang, Wei Shi, James D Chappell, M Gordon Joyce, Yi Zhang, Masaru Kanekiyo, Michelle M Becker, Neeltje van Doremalen, Robert Fischer, Nianshuang Wang, Kizzmekia S Corbett, Misook Choe, Rosemarie D Mason, Joseph G Van Galen, Tongqing Zhou, Kevin O Saunders, Kathleen M Tatti, Lia M Haynes, Peter D Kwong, Kayvon Modjarrad, Wing-Pui Kong, Jason S McLellan, Mark R Denison, Vincent J Munster, John R Mascola, Barney S Graham
Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ∼35% mortality. The potential for a future pandemic originating from animal reservoirs or healthcare-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV. Using a probe-based single B cell-cloning strategy, we have identified and characterized multiple neutralizing mAbs specifically binding to the receptor binding domain (RBD) or S1 (non-RBD) regions from a convalescent MERS-CoV-infected patient and from immunized rhesus macaques...
March 7, 2018: Journal of Virology
Greg Martin, Mairin Boland
The ever-increasing speed and scope of human mobility by international air travel has led to a global transport network for infectious diseases with the potential to introduce pathogens into non-endemic areas, and to facilitate rapid spread of novel or mutated zoonotic agents.Robust national emergency preparedness is vital to mitigate the transmission of infectious diseases agents domestically and to prevent onward spread to other countries. Given the complex range of stakeholders who respond to an infectious disease threat being transmitted through air travel, it is important that protocols be tested and practised extensively in advance of a real emergency...
March 7, 2018: Globalization and Health
Patrick C Y Woo, Susanna K P Lau, Yixin Chen, Emily Y M Wong, Kwok-Hung Chan, Honglin Chen, Libiao Zhang, Ningshao Xia, Kwok-Yung Yuen
Recently, we developed a monoclonal antibody-based rapid nucleocapsid protein detection assay for diagnosis of MERS coronavirus (MERS-CoV) in humans and dromedary camels. In this study, we examined the usefulness of this assay to detect other lineage C betacoronaviruses closely related to MERS-CoV in bats. The rapid MERS-CoV nucleocapsid protein detection assay was tested positive in 24 (88.9%) of 27 Tylonycteris bat CoV HKU4 (Ty-BatCoV-HKU4) RNA-positive alimentary samples of Tylonycteris pachypus and 4 (19...
March 7, 2018: Emerging Microbes & Infections
Maria L Agostini, Erica L Andres, Amy C Sims, Rachel L Graham, Timothy P Sheahan, Xiaotao Lu, Everett Clinton Smith, James Brett Case, Joy Y Feng, Robert Jordan, Adrian S Ray, Tomas Cihlar, Dustin Siegel, Richard L Mackman, Michael O Clarke, Ralph S Baric, Mark R Denison
Emerging coronaviruses (CoVs) cause severe disease in humans, but no approved therapeutics are available. The CoV nsp14 exoribonuclease (ExoN) has complicated development of antiviral nucleosides due to its proofreading activity. We recently reported that the nucleoside analogue GS-5734 (remdesivir) potently inhibits human and zoonotic CoVs in vitro and in a severe acute respiratory syndrome coronavirus (SARS-CoV) mouse model. However, studies with GS-5734 have not reported resistance associated with GS-5734, nor do we understand the action of GS-5734 in wild-type (WT) proofreading CoVs...
March 6, 2018: MBio
Daniel K W Chu, Kenrie P Y Hui, Ranawaka A P M Perera, Eve Miguel, Daniela Niemeyer, Jincun Zhao, Rudragouda Channappanavar, Gytis Dudas, Jamiu O Oladipo, Amadou Traoré, Ouafaa Fassi-Fihri, Abraham Ali, Getnet F Demissié, Doreen Muth, Michael C W Chan, John M Nicholls, David K Meyerholz, Sulyman A Kuranga, Gezahegne Mamo, Ziqi Zhou, Ray T Y So, Maged G Hemida, Richard J Webby, Francois Roger, Andrew Rambaut, Leo L M Poon, Stanley Perlman, Christian Drosten, Veronique Chevalier, Malik Peiris
Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. Although MERS-CoV infection is ubiquitous in dromedaries across Africa as well as in the Arabian Peninsula, zoonotic disease appears confined to the Arabian Peninsula. MERS-CoVs from Africa have hitherto been poorly studied. We genetically and phenotypically characterized MERS-CoV from dromedaries sampled in Morocco, Burkina Faso, Nigeria, and Ethiopia...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Myoung-Don Oh, Wan Beom Park, Sang-Won Park, Pyoeng Gyun Choe, Ji Hwan Bang, Kyoung-Ho Song, Eu Suk Kim, Hong Bin Kim, Nam Joong Kim
Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in 2012. The 2015 Korea outbreak of MERSCoV involved 186 cases, including 38 fatalities. A total of 83% of transmission events were due to five superspreaders, and 44% of the 186 MERS cases were the patients who had been exposed in nosocomial transmission at 16 hospitals. The epidemic lasted for 2 months and the government quarantined 16,993 individuals for 14 days to control the outbreak. This outbreak provides a unique opportunity to fill the gap in our knowledge of MERS-CoV infection...
March 2018: Korean Journal of Internal Medicine
Yujeong Kim
BACKGROUND: This study aimed to identify nurses' experiences of care for patients with Middle East respiratory syndrome-coronavirus (MERS-CoV). Their experiences can be useful to establish a safer healthcare system in preparation for infectious disease outbreaks. METHODS: Data were collected through in-depth individual interviews and analyzed using Colaizzi's phenomenological method. Participants were 12 nurses. RESULTS: Nurses' experiences of care for patients with MERS-CoV were categorized as follows: "Going into a dangerous field," "Strong pressure because of MERS-CoV," "The strength that make me endure," "Growth as a nurse," and "Remaining task...
March 1, 2018: American Journal of Infection Control
Mun Peak Nyon, Lanying Du, Chien-Te Kent Tseng, Christopher A Seid, Jeroen Pollet, Kevin S Naceanceno, Anurodh Agrawal, Abdullah Algaissi, Bi-Hung Peng, Wanbo Tai, Shibo Jiang, Maria Elena Bottazzi, Ulrich Strych, Peter J Hotez
Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 2040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. To address this need, we are developing a subunit recombinant protein vaccine comprising residues 377-588 of the MERS-CoV spike protein receptor-binding domain (RBD), which, when formulated with the AddaVax adjuvant, it induces a significant neutralizing antibody response and protection against MERS-CoV challenge in vaccinated animals...
February 26, 2018: Vaccine
Aasiyah Chafekar, Burtram C Fielding
Human coronaviruses cause both upper and lower respiratory tract infections in humans. In 2012, a sixth human coronavirus (hCoV) was isolated from a patient presenting with severe respiratory illness. The 60-year-old man died as a result of renal and respiratory failure after admission to a hospital in Jeddah, Saudi Arabia. The aetiological agent was eventually identified as a coronavirus and designated Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV has now been reported in more than 27 countries across the Middle East, Europe, North Africa and Asia...
February 24, 2018: Viruses
Joseph Prescott, Darryl Falzarano, Emmie de Wit, Kath Hardcastle, Friederike Feldmann, Elaine Haddock, Dana Scott, Heinz Feldmann, Vincent Jacobus Munster
Middle East respiratory syndrome coronavirus (MERS-CoV) has recently emerged in the Middle East. Since 2012, there have been approximately 2,100 confirmed cases, with a 35% case fatality rate. Disease severity has been linked to patient health status, as people with chronic diseases or an immunocompromised status fare worse, although the mechanisms of disease have yet to be elucidated. We used the rhesus macaque model of mild MERS to investigate whether the immune response plays a role in the pathogenicity in relation to MERS-CoV shedding...
2018: Frontiers in Immunology
Meriadeg Ar Gouilh, Sébastien J Puechmaille, Laure Diancourt, Mathias Vandenbogaert, Jordi Serra-Cobo, Marc Lopez Roïg, Paul Brown, François Moutou, Valérie Caro, Astrid Vabret, Jean-Claude Manuguerra
The emergence of SARS-CoV and MERS-CoV, triggered the discovery of a high diversity of coronaviruses in bats. Studies from Europe have shown that coronaviruses circulate in bats in France but this reflects only a fraction of the whole diversity. In the current study the diversity of coronaviruses circulating in western Europe was extensively explored. Ten alphacoronaviruses in eleven bat species belonging to the Miniopteridae, Vespertilionidae and Rhinolophidae families and, a SARS-CoV-related Betacoronavirus in Rhinolophus ferrumequinum were identified...
February 23, 2018: Virology
Chao Wang, Shuai Xia, Peiyu Zhang, Tianhong Zhang, Weicong Wang, Yangli Tian, Guangpeng Meng, Shibo Jiang, Keliang Liu
The hexameric α-helical coiled-coil formed between the C-terminal and N-terminal heptad repeat (CHR and NHR) regions of class I viral fusion proteins plays an important role in mediating the fusion of the viral and cellular membranes and provides a clear starting point for molecular mimicry that drives viral fusion inhibitor design. Unfortunately, such peptide mimicry of the short α-helical region in the CHR of Middle East respiratory syndrome coronavirus (MERS-CoV) spike protein has been thwarted by the loss of the peptide's native α-helical conformation when taken out of the parent protein structure...
February 21, 2018: Journal of Medicinal Chemistry
Waleed H Mahallawi, Omar F Khabour, Qibo Zhang, Hatim M Makhdoum, Bandar A Suliman
The Middle East respiratory syndrome coronavirus (MERS-CoV) has been recognized as a highly pathogenic virus to humans that infects the respiratory tract and is associated with high morbidity and mortality. Studies in animal models suggest that MERS-CoV infection induces a strong inflammatory response, which may be related to the severity of disease. Data showing the cytokine profiles in humans during the acute phase of MERS-CoV infection are limited. In this study, we have analyzed the profile of cytokine responses in plasma samples from patients with confirmed MERS-CoV infections (n = 7) compared to healthy controls (n = 13)...
February 1, 2018: Cytokine
Ji-Seon Park, Eun-Hyun Lee, No-Rye Park, Young Hwa Choi
BACKGROUND: During an epidemic of a novel infectious disease, many healthcare workers suffer from mental health problems. OBJECTIVES: The aims of this study were to test the following hypotheses: stigma and hardiness exert both direct effects on mental health and also indirect (mediated) effects on mental health through stress in nurses working at a government-designated hospital during a Middle East Respiratory Syndrome coronavirus (MERS-CoV) epidemic. METHODS: A total of 187 participants were recruited using a convenience sampling method...
February 2018: Archives of Psychiatric Nursing
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