• Journal of Microbiology and Biotechnology
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• v.30 no.3
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• pp.427-438
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• 2020

Middle East respiratory syndrome coronavirus (MERS-CoV) infects the lower respiratory airway of humans, leading to severe acute respiratory failure. Unlike human dipeptidyl peptidase 4 (hDPP4), a receptor for MERS-CoV, mouse DPP4 (mDPP4) failed to support MERS-CoV infection. Consequently, diverse transgenic mouse models expressing hDPP4 have been developed using diverse methods, although some models show no mortality and/or only transient and mild-to-moderate clinical signs following MERS-CoV infection. Additionally, overexpressed hDPP4 is associated with neurological complications and breeding difficulties in some transgenic mice, resulting in impeding further studies. Here, we generated stable hDPP4-transgenic mice that were sufficiently susceptible to MERS-CoV infection. The transgenic mice showed weight loss, decreased pulmonary function, and increased mortality with minimal perturbation of overexpressed hDPP4 after MERS-CoV infection. In addition, we observed histopathological signs indicative of progressive pulmonary fibrosis, including thickened alveolar septa, infiltration of inflammatory monocytes, and macrophage polarization as well as elevated expression of profibrotic molecules and acute inflammatory response in the lung of MERS-CoV-infected hDPP4-transgenic mice. Collectively, we suggest that this hDPP4-transgenic mouse is useful in understanding the pathogenesis of MERS-CoV infection and for antiviral research and vaccine development against the virus.

• Journal of Microbiology and Biotechnology
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• v.29 no.6
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• pp.999-1007
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• 2019

Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012 and related infection cases have been reported in over 20 countries. Roughly 10,000 human cases have so far been reported in total with fatality rates at up to 40%. The majority of cases have occurred in Saudi Arabia with mostly sporadic outbreaks outside the country except for the one in South Korea in 2015. The Korean MERS-CoV strain was isolated from the second Korean patient and its genome was fully sequenced and deposited. To develop virus-specific protective and therapeutic agents against the Korean isolate and to investigate molecular determinants of virus-host interactions, it is of paramount importance to generate its full-length cDNA. Here we report that two full-length cDNAs from a Korean patient-isolated MERS-CoV strain were generated by a combination of conventional cloning techniques and efficient Gibson assembly reactions. The full-length cDNAs were validated by restriction analysis and their sequence was verified by Sanger method. The resulting cDNA was efficiently transcribed in vitro and the T7 promoter-driven expression was robust. The resulting reverse genetic system will add to the published list of MERS-CoV cDNAs and facilitate the development of Korean isolate-specific antiviral measures.

• The Journal of the Korea Contents Association
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• v.18 no.7
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• pp.484-494
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• 2018

Middle East Respiratory Syndrome (MERS), which occurred in the Middle East in 2015, is the most acute respiratory infectious disease in Korea. The limitations of the government's ability to respond to the spread of MERS and the inadequate communication of the government to the public have reduced the public's confidence in the government's infectious disease management policy. And it became an opportunity to raise awareness that infectious diseases could easily break down the national anti-virus system. Therefore, this study investigated the emergency response system of the infectious disease in the United States and sought to improve the infection control system in Korea. In order to achieve the purpose of the study, we analyzed the government's response to the MERS in 2015, analyzed the organization structure and role of the US CDC, and IMS.

• Journal of The Korea Institute of Healthcare Architecture
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• v.22 no.3
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• pp.45-56
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• 2016

Purpose: The MERS(Middle East Respiratory Syndrome) outbreaks in Korea highlighted dramatically the failings of traditional hospital environment for controlling or preventing infections among both patients and healthcare workers. MERS is transmitted by droplets that can be airborne over a limited area. The point should be emphasized that MERS in South Korea was predominantly a hospital-acquired (not a community-acquired) infection, because approximately 93% of MERS cases were resulted from exposure in hospital settings. This paper tries to suggest the design guidelines of negative pressured isolation ward for the sake of proper control of severe respiratory infectious diseases. Methods: Literature survey on the design guideline and regulations of airborne infection wards in Korea, Europe U.K. and CDC of U.S. have been carries out. 4 special infection wards in Hongkong, Germany, Japan and Korea have been surveyed in order to make the best use of the experiences related to facility design and operations. Results: Operating system influencing the facility design, space organizations of infectious ward including required space and zoning, and circulations of patients, staffs and materials are proposed. Implications: The results of this paper can be the basic data for the design of the airborne infection ward and relevant regulations. Afterwards in-depth study such as the development of space standards for the single bedroom, locker room and so on could be explored.

• Journal of Microbiology and Biotechnology
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• v.29 no.5
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• pp.813-819
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• 2019

Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe respiratory impairment with a reported mortality rate of ~36% in humans. The absence of clinically available MERS-CoV vaccines and treatments to date has resulted in uncontrolled incidence and propagation of the virus. In vaccine design, fusion with the IgG Fc domain is reported to increase the immunogenicity of various vaccine antigens. However, limited reports have documented the potential negative effects of Fc fusion on vaccine antigens. To determine whether Fc fusion affects the immunogenicity of MERS-CoV antigen, we constructed a Fcassociated MERS-CoV spike protein (eS770-Fc, 110 kDa), whereby human IgG4 Fc domain was fused to MERS-CoV spike protein (eS770) via a Gly/Pro linker using baculovirus as the expression system. For comparative analyses, two eS770 proteins lacking the IgG4 Fc domain were generated using the IdeS protease ($eS770-{\Delta}Fc$) or His tag attachment (eS770-His) and the immunogenicity of the above constructs were examined following intramuscular immunization in mice. Contrary to expectations, non-Fc spike proteins ($eS770-{\Delta}Fc$, eS770-His; 90 kDa) showed higher immunogenicity than the Fc fusion protein (eS770-Fc). Moreover, unlike non-Fc spike proteins, eS770-Fc immunization did not elicit neutralizing antibodies against MERS-CoV. The lower immunogenicity of Fc-fused eS770 was related to alterations in the structural conformation of the spike protein. Taken together, our results indicate that IgG Fc fusion reduces the immunogenicity of eS770 by interfering with the proper folding structure.

• Clinical and Experimental Pediatrics
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• v.63 no.4
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• pp.119-124
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• 2020

A cluster of severe pneumonia of unknown etiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was isolated from lower respiratory tract sample as the causative agent. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 rapidly spread into at least 114 countries and killed more than 4,000 people by March 11 2020. WHO officially declared COVID-19 a pandemic on March 11, 2020. There have been 2 novel coronavirus outbreaks in the past 2 decades. The outbreak of severe acute respiratory syndrome (SARS) in 2002-2003 caused by SARS-CoV had a case fatality rate of around 10% (8,098 confirmed cases and 774 deaths), while Middle East respiratory syndrome (MERS) caused by MERS-CoV killed 861 people out of a total 2,502 confirmed cases between 2012 and 2019. The purpose of this review is to summarize known-to-date information about SARS-CoV-2, transmission of SARS-CoV-2, and clinical features.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.18 no.3
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• pp.175-184
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• 2017

This study was conducted to identify factors influencing turnover intention of nurses that were cohort quarantined during the Middle East Respiratory Syndrome(MERS) outbreak. Subjects of this study were 267 nurses from three hospitals that came in direct or indirect contact with diagnosed MERS and suspected MERS patients and were group quarantined during the 2015 MERS breakout. The data were collected from October 1, 2015 through November 30, 2015. The collected data were evaluated based on descriptive statistics, t-tests, ANOVA and multivariate regression conducted using the SPSS/WIN 21.0 program. The factors influencing turnover intention were work experience and usual stress levels. While nurses tending to MERS patients had the highest stress levels (p<.001), different types of patient care during the MERS outbreak did not yield to a statistically significant turnover intention. Theresults of this study indicate that work experience and usual stress levels impact turnover intention of nurses and because the stress resulting from the MERS outbreak did not significantly affect the turnover intention, further human resource management is required to reduce the usual stress levels of nurses.

• Pediatric Infection and Vaccine
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• v.27 no.1
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• pp.1-10
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• 2020

A cluster of severe pneumonia of unknown etiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was isolated from lower respiratory tract sample as the causative agent. The current outbreak of infections with SARS-CoV-2 is termed coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 rapidly spread into at least 114 countries and killed more than 4,000 people by March 11, 2020. WHO officially declared COVID-19 a pandemic on March 11, 2020. There have been 2 novel coronavirus outbreaks in the past 2 decades. The outbreak of severe acute respiratory syndrome (SARS) in 2002-2003 caused by SARS-CoV had a case fatality rate of around 10% (8,098 confirmed cases and 774 deaths), while Middle East respiratory syndrome (MERS) caused by MERS-CoV killed 858 people out of a total 2,499 confirmed cases between 2012 and 2019. The purpose of this review is to summarize known-to-date information about SARS-CoV-2, transmission of SARS-CoV-2, and clinical features of COVID-19.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.311-319
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• 2020

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a newly emerging viral disease with fatal outcomes. However, no MERS-CoV-specific treatment is commercially available. Given the absence of previous structure-based drug discovery studies targeting MERS-CoV fusion proteins, this set of compounds is considered the first generation of MERS-CoV small molecule fusion inhibitors. After a virtual screening campaign of 1.56 million compounds followed by cell-cell fusion assay and MERS-CoV plaques inhibition assay, three new compounds were identified. Compound numbers 22, 73, and 74 showed IC₅₀ values of 12.6, 21.8, and 11.12 µM, respectively, and were most effective at the onset of spike-receptor interactions. The compounds exhibited safe profiles against Human embryonic kidney cells 293 at a concentration of 20 µM with no observed toxicity in Vero cells at 10 µM. The experimental results are accompanied with predicted favorable pharmacokinetic descriptors and drug-likeness parameters. In conclusion, this study provides the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range.

• IMMUNE NETWORK
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• v.20 no.4
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• pp.28.1-28.25
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• 2020

The recent emergence of the novel coronavirus (CoV) or severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a global threat to human health and economy. As of June 26, 2020, over 9.4 million cases of infection, including 482,730 deaths, had been confirmed across 216 countries. To combat a devastating virus pandemic, numerous studies on vaccine development are urgently being accelerated. In this review article, we take a brief look at the characteristics of SARS-CoV-2 in comparison to SARS and Middle East respiratory syndrome (MERS)-CoVs and discuss recent approaches to coronavirus disease-2019 (COVID-19) vaccine development.