• Journal of Microbiology and Biotechnology
• /
• 제30권3호
• /
• 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.

• Journal of Microbiology and Biotechnology
• /
• 제29권6호
• /
• 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.

• 한국콘텐츠학회논문지
• /
• 제18권7호
• /
• pp.484-494
• /
• 2018

2015년 중동지역에서 발생한 메르스(Middle East Respiratory Syndrome, MERS)는 주요 발병국인 사우디아라비아를 제외하고 세계적으로 우리나라에 가장 큰 피해를 입힌 급성 호흡기 감염병이다. 메르스 사태는 인명피해뿐만 아니라 국민적 불안감과 막대한 경제적 피해를 가져왔으며, 정부의 감염병 위기관리 체계의 문제점을 여실히 보여주었다. 정부의 메르스 확산에 대한 대응능력의 한계와 국민을 대상으로 하는 정부의 커뮤니케이션 미흡 등은 정부의 감염병 위기관리 정책에 대한 국민의 신뢰를 저하시켰으며, 감염병으로 인해 국가의 방역망 체계가 쉽게 무너질 수 있다는 경각심을 불러일으키는 계기가 되었다. 이에 본 연구는 미국의 감염병 긴급대응체계를 고찰하여 우리나라 감염병 위기관리 체계의 개선방안을 모색하였다. 연구목적을 달성하기 위하여, 2015년 정부의 메르스 대응현황을 살펴보았다. 그리고 미국 CDC의 EOC 조직 구성 및 역할과 IMS 등을 분석하였다.

• 의료ㆍ복지 건축 : 한국의료복지건축학회 논문집
• /
• 제22권3호
• /
• pp.45-56
• /
• 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
• /
• 제29권5호
• /
• 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.

• Clinical and Experimental Pediatrics
• /
• 제63권4호
• /
• pp.119-124
• /
• 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.

• 한국산학기술학회논문지
• /
• 제18권3호
• /
• pp.175-184
• /
• 2017

본 연구는 메르스 대유행 시 코호트 격리된 병원 간호사의 이직의도 영향요인을 확인하여 추후 감염병 유행 시 간호사 인적관리를 위한 기초자료를 제공하고자 시행되었다. 연구대상자는 메르스 대유행 시에 코호트 격리된 3개의 병원에서 메르스 확진환자나 의심환자 간호에 직접 참여하였거나, 메르스 확진 혹은 의심환자를 직접 돌보지는 않았으나 이들 환자가 있는 병동 혹은 병원에 근무한 267명의 간호사이다. 원 자료의 수집은 2015년 10월 1일부터 11월 30일까지 이루어졌으며, 수집된 자료는 SPSS/WIN 21.0을 사용하여 빈도와 백분율, t-test, ANOVA 및 다중 회귀분석을 실시하였다. 본 연구에서 대상자의 이직의도에 영향을 미치는 요인은 근무기간과 평소 스트레스로 나타났으며, 메르스 확진환자를 직접 간호한 간호사들의 경우 높은 메르스 스트레스를 경험하였음에도 불구하고(p<.001) 이직의도에는 통계적으로 유의한 영향을 미치지 않았다. 본 연구결과에서 주목해야 할 부분은 치명적인 감염을 야기할 수 있는 메르스 환자 간호에 직 간접적으로 참여한 간호사가 경험한 메르스 스트레스보다 평소 스트레스가 이직의도에 유의한 영향을 미친다는 점이다. 따라서 간호사의 이직의도를 감소시키고, 성공적인 인력관리를 위해서는 감염성 질환과 관련된 특수한 상황에서의 간호사의 스트레스 관리 뿐 아니라 평소 직무특성을 고려한 스트레스 완화에 더 많은 관심을 가질 필요가 있는 것으로 나타났다.

• Pediatric Infection and Vaccine
• /
• 제27권1호
• /
• pp.1-10
• /
• 2020

2019년 12월에 중국 후베이성 우한시에서 원인 미상 폐렴이 무리 지어 발생하기 시작하였다. 환자의 하기도에서 이전에 알려지지 않은 새로운 코로나바이러스가 분리되었으며 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)로 명명되었다. 세계보건기구는 SARS-CoV-2에 의한 질병을 코로나바이러스감염증-19(coronavirus disease 2019, COVID-19)로 명명하였다. 2020년 3월 11일에 COVID-19는 전세계 최소 114국으로 퍼졌으며 약 4,000명이 사망하여 세계보건기구는 COVID-19가 세계적 대유행임을 선언하였다. 지난 20년 동안 새로운 코로나바이러스에 의한 두 번의 유행이 있었다. 2002-2003년 중증급성호흡기증후군(severe acute respiratory syndrome, SARS) 유행 시에는 8,098명의 확진 환자와 774명의 사망자가 발생하였으며, 2012년에 사우디 아라비아에서 시작되어 현재까지 주로 아라비아 반도에서 발생하고 있는 중동호흡기증후군(Middle East respiratory syndrome, MERS)는 2019년까지 총 2,499명의 환자와 858명의 사망자를 발생시켰다. 본 종설의 목적은 2020년 3월 12일까지 알려진 SARS-CoV-2의 특징과 전파 양상 및 COVID-19의 임상 증상을 알아보고 SARS와 MERS와의 유사점 및 차이점에 대하여 간략하게 소개하는 것이다.

• Biomolecules & Therapeutics
• /
• 제28권4호
• /
• 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.

• IMMUNE NETWORK
• /
• 제20권4호
• /
• pp.28.1-28.25
• /
• 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.