• Pediatric Infection and Vaccine
• /
• v.22 no.3
• /
• pp.143-146
• /
• 2015

Since 2012, outbreaks of the Middle East respiratory coronavirus (MERS-CoV) have been reported, including the Republic of Korea. To date, most of the people infected with the virus are adults. Herein we describe the clinical characteristics of cases of MERS-CoV infection among children. As of October 29, 2015, MERS-CoV has caused 34 pediatric infections, which accounts for 2.1% of all cases. The median age was 13 years (range 9 months to 17 years) and where gender has been reported (n=33), 57.6% cases were male. About half of the patients were asymptomatic and the majority of the symptomatic patients had respiratory symptoms. In general, the clinical outcome in children was favorable. Among the four patients who died of progressive pneumonia, three had documented comorbidities. MERS-CoV infection in children has a lower incidence and mortality compared to adults.

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

• Korean Journal of Occupational Health Nursing
• /
• v.25 no.1
• /
• pp.1-8
• /
• 2016

Purpose: The 2015 Korean Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreaks resulted in 186 cases, with 8% (15 persons) of these being nurses. This study aimed to examine MERS-CoV infection status of clinical nurses and to evaluate perception for infection control. Methods: We investigated the MERS-CoV infection status of nurses using MERS-CoV press release data. We examined and analysed perception for Infection control of 121 nurses of the three MERS intensive therapeutic hospitals in July 2015. Results: One to six nurses per hospital in total 8 health care facilities were infected with MERS-CoV. They mainly had short clinical careers and were unaware of infection possibility. The personal and organizational infection control levels that nurses perceive were low and the relationship between two levels was statistically significant. Conclusion: For promoting health protection and infectious disease management competency of nurses, it is necessary to prepare institutional system for controlling infectious disease.

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

• BMB Reports
• /
• v.52 no.6
• /
• pp.397-402
• /
• 2019

Middle East respiratory syndrome coronavirus (MERS-CoV) uses the spike (S) glycoprotein to recognize and enter target cells. In this study, we selected two epitope peptide sequences within the receptor binding domain (RBD) of the MERS-CoV S protein. We used a complex consisting of the epitope peptide of the MERS-CoV S protein and CpG-DNA encapsulated in liposome complex to immunize mice, and produced the monoclonal antibodies 506-2G10G5 and 492-1G10E4E2. The western blotting data showed that both monoclonal antibodies detected the S protein and immunoprecipitated the native form of the S protein. Indirect immunofluorescence and confocal analysis suggested strong reactivity of the antibodies towards the S protein of MERS-CoV virus infected Vero cells. Furthermore, the 506-2G10G5 monoclonal antibody significantly reduced plaque formation in MERS-CoV infected Vero cells compared to normal mouse IgG and 492-1G10E4E2. Thus, we successfully produced a monoclonal antibody directed against the RBD domain of the S protein which could be used in the development of diagnostics and therapeutic applications in the future.

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

• Journal of Korean Medical Science
• /
• v.33 no.53
• /
• pp.348.1-348.6
• /
• 2018

We report a case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in a 61-year-old businessman returning from Kuwait. The patient arrived there on August 16, 2018, developed watery diarrhea on August 28 (day 0), and came back to Korea on September 7 (day 10) as his condition worsened. Upon arrival, he complained of diarrhea and weakness, but denied any respiratory symptoms, and he directly went to visit an emergency room. Chest radiography revealed interstitial infiltrates in the lungs, and he was immediately transferred to an isolation unit. Quantitative real-time PCR analysis of sputum samples taken on day 11 returned positive for MERS-CoV. No secondary MERS-CoV infection was identified among people who had close contact with him. This case underscores the importance of a high index of suspicion of MERS-CoV infection in any febrile patients who present after a trip to the Middle East.

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

• Korean Journal of Health Education and Promotion
• /
• v.32 no.3
• /
• pp.1-9
• /
• 2015

Objectives: The purpose of this article was to assess epidemiological characteristics and recommendations for strengthening national response and preparedness after MERS-CoV outbreak in Korea, 2015. Methods: The author reviewed epidemiological reports and policy recommendations on MERS-CoV outbreak in Korea, 2015. Results: There was no evidence that genetical difference between the MERS viruses in the Republic of Korea and recent viruses in the Middle East. From the index case to last laboratory-confirmed case, there were 186 laboratory-confirmed cases that included 36 deaths(19.4%), all of whom appear epidemiologically linked to the index cases or subsequent secondary, tertiary, and quaternary cases. This outbreak spread to hospitals through nosocomial transmission. At least, three large clusters were investigated. However, there was at least one case of community transmission of MERS-CoV. Several factors had contributed to the MERS outbreak in Korea, 2015 that including epidemiological characteristics, and infrastructure of national healthcare system for preventing and controlling emerging infectious diseases. Conclusions: It is very important that to share experiences and identify underlying causes of this outbreak for prevention and control of emerging infectious disease in the future; including epidemiology, clinical features, and public health response and preparedness.

• Genomics & Informatics
• /
• v.18 no.3
• /
• pp.30.1-30.7
• /
• 2020

The novel coronavirus pandemic that has originated from China and spread throughout the world in three months. Genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) predecessor, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) play an important role in understanding the concept of genetic variation. In this paper, the genomic data accessed from National Center for Biotechnology Information (NCBI) through Molecular Evolutionary Genetic Analysis (MEGA) for statistical analysis. Firstly, the Bayesian information criterion (BIC) and Akaike information criterion (AICc) are used to evaluate the best substitution pattern. Secondly, the maximum likelihood method used to estimate of transition/transversions (R) through Kimura-2, Tamura-3, Hasegawa-Kishino-Yano, and Tamura-Nei nucleotide substitutions model. Thirdly and finally nucleotide frequencies computed based on genomic data of NCBI. The results indicate that general times reversible model has the lowest BIC and AICc score 347,394 and 347,287, respectively. The transition/transversions bias for nucleotide substitutions models varies from 0.56 to 0.59 in MEGA output. The average nitrogenous bases frequency of U, C, A, and G are 31.74, 19.48, 28.04, and 20.74, respectively in percentages. Overall the genomic data analysis of SARS-CoV-2, SARS-CoV, and MERS-CoV highlights the close genetic relationship.