• BMB Reports
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• 제56권11호
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• pp.606-611
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• 2023

The main protease (Mpro) of SARS-CoV-2 cleaves 11 sites of viral polypeptide chains and generates essential non-structural proteins for viral replication. Mpro is an important drug target against COVID-19. In this study, we developed a real-time fluorometric turn-on assay system to evaluate Mpro proteolytic activity for a substrate peptide between NSP4 and NSP5. It produced reproducible and reliable results suitable for HTS inhibitor assays. Thus far, most inhibitors against Mpro target the active site for substrate binding. Mpro exists as a dimer, which is essential for its activity. We investigated the potential of the Mpro dimer interface to act as a drug target. The dimer interface is formed of domain II and domain III of each protomer, in which N-terminal ten amino acids of the domain I are bound in the middle as a sandwich. The N-terminal part provides approximately 39% of the dimer interface between two protomers. In the real-time fluorometric turn-on assay system, peptides of the N-terminal ten amino acids, N10, can inhibit the Mpro activity. The dimer interface could be a prospective drug target against Mpro. The N-terminal sequence can help develop a potential inhibitor.

• Bulletin of the Korean Chemical Society
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• 제31권1호
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• pp.87-91
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• 2010

For the discovery of new antivirals against Severe Acute Respiratory Syndrome-coronavirus (SARS-CoV), we prepared and evaluated several benzoquinoline compounds as its 3C-like protease (3CLpro) inhibitors. Based on the computer modeling study that each of the two rigid benzoquinolinone and N-phenoltetrazole moieties of the compound 1 is bound to the S1 and S2 sites, respectively, of the SARS protease by forming H-bonds and hydrophobic interactions, we designed and synthesized alkylated benzoquinolines at both the sites of the hydroxyl groups. We found that the compound 2a showed five times higher inhibiting activity against the 3CLpro compared to the compound 1.

• Pediatric Infection and Vaccine
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• 제29권2호
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• pp.70-76
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• 2022

코로나바이러스감염증-19 (COVID-19)의 임상 양상은 무증상부터 급성 호흡곤란 증후군에 이르기까지 다양하다. 점액 다당류증(mucopolysaccharidosis) 2형은글라이코스아미노글라이칸(glycosaminoglycan)의 일종인 헤파란 황산염(heparan sulfate)과 더마탄 황산염(dermatan sulfate)의 분해를 촉매하는 효소 결핍에 의해 상기 물질이 리소좀(lysosome)에 축적되는 질환으로 전신 침범, 특히 호흡기침범을 특징으로 한다. 따라서 박테리아나 바이러스에 의한 호흡기 감염은 예후에 치명적일 수 있다. 현재 점액 다당류증 환자에서 제 2형 중증급성호흡기증후군 코로나 바이러스(SARS-CoV-2) 감염 후의 임상 양상에 대한 보고는 매우 드물고, 이에 점액 다당류증 2형으로 효소대체요법을 받고 있던 환자에서 상기 바이러스 감염 후의 임상 양상에 대해 보고하고 관련 문헌에 대해 고찰하고자 한다. 16세 남아로 가족간 전파로 코로나바이러스감염증이 발생하였다. 콧물, 기침, 가래 등 호흡기 증상이 관찰되었다. 발열이나 산소요구도 증가는 없었으며 심박수, 호흡수, 산소 포화도는 정상 범위였고 혈액검사결과에서 백혈구 감소증이 관찰되었다. 흉부 방사선 사진에서 폐렴 소견은 보이지 않았다. 보존적 치료와 격리만으로 증상이 호전되었다. 경미한 임상 양상의 원인으로 전구 물질의 축적으로 인해 바이러스에게 불리한 숙주의 세포 환경, 바이러스와의 상호작용에 관여하는 단백질을 암호화하는 유전자 발현의 특정방향으로의 변화가 제시되고 있다. 또한 점액 다당류증 환자에서 증가된 혈청 헤파란 황산염이 SARS-CoV-2 스파이크 단백질과 숙주 세포의 상호작용에 필수적인 세포 표면의 헤파란 황산염과 경쟁하여 SARS-CoV-2의 세포 내 침투로부터 보호한다는 가설도 있다. 향후 더 많은 사례를 통해 점액 다당류증 등의 리소좀 축적질환에서 코로나바이러스감염증의 발현 양상에 대한 연구가 필요하다.

• Pediatric Infection and Vaccine
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• 제28권2호
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• pp.66-81
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• 2021

코로나바이러스감염증-19는 전 세계적으로 유행하고 있으며, 2021년 7월 15일 기준으로 1.88억명 이상의 확진자와 406만명 이상의 사망자가 발생하였다. 소아청소년에서는 성인에 비해 비교적 중증 감염 발생이 낮으나, 일부에서는 SARS-CoV-2 감염 약 2-6주후소아다기관염증증후군(multisystem inflammatory syndrome in children, MIS-C)라는 합병증이 발생할 수 있다. MIS-C는 어린영아부터 청소년까지 다양한 연령에서 발생할 수 있으며, 발열을 포함하여 다양한 장기와 관련된 증상을 보일 수 있다. 소화기 및 신경계 증상이 흔하며, 많은 경우 가와사키병과 유사한 피부점막증상 등이 나타난다. 특히 심장관련 증상으로 좌심실 기능저하, 심근염 등이 나타날 수 있으며, 관상동맥확장 및 관상동맥류가 나타날 수 있다. 경우에 따라 저혈압, 쇼크를 동반하며, 중환자실 치료 및 기계환기요법을 요하나, 적절한 치료 후 대체로 회복을 보이는 것으로 보고된다. 이와 같이 MIS-C는 소아청소년에서 SARS-CoV-2 이후 드물게 발생하는 중요한 합병증으로, 임상증상을 잘 인지하고 조기에 적절한 치료를 하는 것이 중요하다. 이에 본 종설에서는 MIS-C의 역학 및 임상 증상, 추정되는 병태생리, 진단적 접근 및 치료에 대해 다루고자 한다.

• Tuberculosis and Respiratory Diseases
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• 제86권2호
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• pp.142-149
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• 2023

Background: Coronavirus disease 2019 (COVID-19) is an ongoing global public health threat and different variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified. This study aimed to analyse the factors associated with negative conversion of polymerase chain reaction (PCR) and prognosis in critically ill patients according to the SARS-CoV-2 variant. Methods: This study retrospectively analysed 259 critically ill patients with COVID-19 who were admitted to the intensive care unit of a tertiary medical center between January 2020 and May 2022. The Charlson comorbidity index (CCI) was used to evaluate comorbidity, and a negative PCR test result within 2 weeks was used to define negative PCR conversion. The cases were divided into the following three variant groups, according to the documented variant of SARS-CoV-2 at the time of diagnosis: non-Delta (January 20, 2020-July 6, 2021), Delta (July 7, 2021- January 1, 2022), and Omicron (January 30, 2022-April 24, 2022). Results: The mean age of the 259 patients was 67.1 years and 93 (35.9%) patients were female. Fifty (19.3%) patients were smokers, and 50 (19.3%) patients were vaccinated. The CCI (hazard ratio [HR], 1.555; p<0.001), vaccination (HR, 0.492; p=0.033), and Delta variant (HR, 2.469; p=0.002) were significant factors for in-hospital mortality. The Delta variant (odds ratio, 0.288; p=0.003) was associated with fewer negative PCR conversion; however, vaccination (p=0.163) and remdesivir (p=0.124) treatments did not. Conclusion: The Delta variant of SARS-CoV-2 is associated with lower survival and negative PCR conversion. Contrary to expectations, vaccination and remdesivir may not affect negative PCR conversion in critically ill patients with COVID-19.

• Clinical and Experimental Pediatrics
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• 제64권6호
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• pp.280-281
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• 2021

• Clinical and Experimental Vaccine Research
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• 제12권3호
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• pp.262-263
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• 2023

• Clinical and Experimental Vaccine Research
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• 제12권1호
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• pp.85-86
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• 2023

• Pediatric Infection and Vaccine
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• 제29권2호
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• pp.61-69
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• 2022

Coronavirus disease 2019 (COVID-19) has been a global pandemic for over 2 years. During the Omicron (B.1.1.529) variant-predominant period in South Korea, confirmed cases among children and adolescents surged. This review found that, although younger children may be less susceptible to COVID-19 than adolescents, more research is needed on the role of children and adolescents in the disease's spread. Detailed epidemiological information about the transmissibility of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain in children and adolescents is currently scarce, and more research is needed on the role of children and adolescents in disease's spread. There may be a difference in the proportion of cases with severe disease requiring hospitalization depending on the dominant mutant strain; however, COVID-19 generally presents with a mild-to-moderate course in children aged 5-11 years old.

• Bulletin of the Korean Chemical Society
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• 제30권8호
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• pp.1724-1728
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• 2009

Severe acute respiratory syndrome coronavirus (SARS-CoV) helicase separates the double-stranded nucleic acids using the energy from ATP hydrolysis. We have measured ATPase activity of SARS-CoV helicase in the presence of various types of nucleic acids. Steady state ATPase analysis showed that poly(U) has two-times higher turnover number than poly(C) with lower Michaelis constant. When M13 single-stranded DNA is used as substrate, the Michaelis constant was about twenty-times lower than poly(U), whereas turnover numbers were similar. However, stimulation of ATPase activity was not observed in the presence of double-stranded DNA. pH dependent profiles of ATP hydrolysis with the helicase showed that the optimal ATPase activities were in a range of pH 6.2 ~ 6.6. In addition, ATP hydrolysis activity assays performed in the presence of various divalent cations exhibited that $Mg^{2+}$ stimulated the ATPase activity with the highest rate and $Mn^{2+}$ with about 40% rate as compared to the $Mg^{2+}$.