• Journal of Microbiology and Biotechnology
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• 제29권6호
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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.

• Molecules and Cells
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• 제43권11호
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• pp.953-963
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• 2020

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an infectious disease with multiple severe symptoms, such as fever over 37.5℃, cough, dyspnea, and pneumonia. In our research, microRNAs (miRNAs) binding to the genome sequences of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory-related coronavirus (MERS-CoV), and SARS-CoV-2 were identified by bioinformatic tools. Five miRNAs (hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-16-5p, and hsa-miR-196a-1-3p) were found to commonly bind to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also identified miRNAs that bind to receptor proteins, such as ACE2, ADAM17, and TMPRSS2, which are important for understanding the infection mechanism of SARS-CoV-2. The expression patterns of those miRNAs were examined in hamster lung samples infected by SARS-CoV-2. Five miRNAs (hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-221-3p, hsa-miR-140-3p, and hsa-miR-422a) showed differential expression patterns in lung tissues before and after infection. Especially, hsa-miR-15b-5p and hsa-miR-195-5p showed a large difference in expression, indicating that they may potentially be diagnostic biomarkers for SARS-CoV-2 infection.

• 보건교육건강증진학회지
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• 제32권3호
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• pp.1-9
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• 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.

• Journal of Microbiology and Biotechnology
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• 제30권3호
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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.

• 약학회지
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• 제59권6호
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• pp.245-250
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• 2015

Middle East respiratory syndrome - coronavirus infection has posed substantial threat to public health with extremely high mortality rate in 2015. Although there are no approved novel medications for coronavirus, several antiviral agents such as ribavirin and interferon have been tried to MERS patients according to the in-vitro inhibitory effect, therapeutic effect on the animal model and experience from the severe acute respiratory syndrome - coronavirus infection. The aim of this study is to evaluate the clinical evidence of the antiviral treatment for MERS-CoV infection. After systematically searching the medical literature databases, I found five studies described the clinical efficacy of antiviral treatment on MERS patients. All of them were about the combination therapy of ribavirin and interferon (IFN). Two of them were retrospective cohort studies with quality of evidence (QOE) II and the others were observational study and case reports with QOE III. As a result of critical appraisal, it is concluded that none of those studies represented confirmatory clinical evidence of the efficacy of ribavirin and interferon combination therapy on MERS patients. Although Omrani et al. represented that ribavirin and IFN treatment had significantly improved survival at 14 days, it was not enough time to conclude the effect.

• Journal of Microbiology and Biotechnology
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• 제29권8호
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• pp.1316-1323
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• 2019

Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging coronavirus which is zoonotic from bats and camels. Its infection in humans can be fatal especially in patients with preexisting conditions due to smoking and chronic obstructive pulmonary disease (COPD). Among the 25 proteins encoded by MERS-CoV, 5 accessory proteins seem to be involved in viral evasion of the host immune responses. Here we report that ORF4a, ORF4b, and ORF8b proteins, alone or in combination, effectively antagonize nuclear factor kappa B ($NF-{\kappa}B$) activation. Interestingly, the inhibition of $NF-{\kappa}B$ by MERS-CoV accessory proteins was mostly at the level of pattern recognition receptors: melanoma differentiation-associated gene 5 (MDA5). ORF4a and ORF4b additively inhibit MDA5-mediated activation of $NF-{\kappa}B$ while that of retinoic acid-inducible gene 1 (RIG-I) is largely not perturbed. Of note, ORF8b was found to be a novel antagonist of MDA5-mediated $NF-{\kappa}B$ activation. In addition, ORF8b also strongly inhibits Tank-binding kinase 1 (TBK1)-mediated induction of $NF-{\kappa}B$ signaling. Taken together, MERS-CoV accessory proteins are involved in viral escape of $NF-{\kappa}B$-mediated antiviral immune responses.

• 정보관리학회지
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• 제32권4호
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• pp.273-287
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• 2015

본 연구는 국민들에게 불안감을 야기하고 전반적인 사회활동을 위축시키는 메르스와 같은 질병의 유행이 공공도서관의 이용에 어떠한 영향을 주는지 알아보고자 하였다. 이를 위해 국립세종도서관에 위치하고 있는 "공공도서관 빅데이터 수집 및 분석 플랫폼"을 통해 전국 303개 공공도서관에서 수집된 18,711,453건의 대출기록을 분석하였다. 분석 결과는 다음과 같다. 첫째, 메르스가 유행했던 2015년도는 64,645.05권으로 2014년보다 하루 평균 6,300권 가량 대출책수가 감소하였다. 둘째, 2014년의 경우 7월 5일부터 8월 19일까지의 일평균 대출책수가 4월 4일부터 5월 19일까지와 5월 20일부터 7월 4일까지보다 많은 것으로 나타났다. 이는 학생들의 여름방학이 공공도서관의 대출책수 증가에 영향을 주었을 것으로 파악할 수 있다. 셋째, 메르스가 발생했던 2015년의 경우 메르스 유행 후 기간의 일평균 대출책수가 메르스 유행기간인 5월 20일부터 7월 4일까지보다 많은 것으로 나타났으나 메르스 유행 전 기간과는 유의한 차이가 존재하지 않았다. 넷째, 2014년과 2015년의 메르스 유행 전 기간의 일평균 대출책수와 2014년과 2015년의 메르스 유행 기간의 일평균 대출책수에는 유의한 차이가 없었으나, 2014년과 2015년의 메르스 유행 후 기간의 일평균 대출책수에서는 유의한 차이가 있었다. 연구 결과 국민들에게 불안감을 가져다 준 메르스는 질병의 유행 기간 보다는 오히려 유행 후 기간 동안 공공도서관의 일평균 대출책수에 영향을 주었음을 확인할 수 있었다.

• Journal of Microbiology and Biotechnology
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• 제29권5호
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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.

• Journal of Preventive Medicine and Public Health
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• 제49권1호
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• pp.1-17
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• 2016

The Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 has drawn public attention regarding the legal regulation of infectious disease control in Korea. This paper discusses the interpretive and legislative concerns regarding the Infectious Disease Prevention and Control Act, its ordinance and enforcement regulations, as well as public statements from the relevant administrative agency. Future improvements are also proposed.

• Journal of Preventive Medicine and Public Health
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• 제48권6호
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• pp.271-273
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• 2015

Quaternary prevention should be implemented to minimize harm to patients because the ultimate goal of medicine is to prevent disease and promote health. Primary care physicians have a major responsibility in quaternary prevention, and the establishment of clinical epidemiology as a distinct field of study would create a role charged with minimizing patient harm arising from over-medicalization.