• Title/Summary/Keyword: Severe acute respiratory syndrome coronavirus 2

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ATP Hydrolysis Analysis of Severe Acute Respiratory Syndrome (SARS) Coronavirus Helicase

  • Lee, Na-Ra;Lee, A-Ram;Lee, Bok-Hui;Kim, Dong-Eun;Jeong, Yong-Joo
    • Bulletin of the Korean Chemical Society
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    • v.30 no.8
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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 $Mg^{2+}$.

Cryo-EM as a powerful tool for drug discovery: recent structural based studies of SARS-CoV-2

  • Han‑ul Kim;Hyun Suk Jung
    • Applied Microscopy
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    • v.51
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    • pp.13.1-13.7
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    • 2021
  • The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has arisen as a global pandemic affecting the respiratory system showing acute respiratory distress syndrome (ARDS). However, there is no targeted therapeutic agent yet and due to the growing cases of infections and the rising death tolls, discovery of the possible drug is the need of the hour. In general, the study for discovering therapeutic agent for SARS-CoV-2 is largely focused on large-scale screening with fragment-based drug discovery (FBDD). With the recent advancement in cryo-electron microscopy (Cryo-EM), it has become one of the widely used tools in structural biology. It is effective in investigating the structure of numerous proteins in high-resolution and also had an intense influence on drug discovery, determining the binding reaction and regulation of known drugs as well as leading the design and development of new drug candidates. Here, we review the application of cryo-EM in a structure-based drug design (SBDD) and in silico screening of the recently acquired FBDD in SARS-CoV-2. Such insights will help deliver better understanding in the procurement of the effective remedial solution for this pandemic.

Mitochondrial Location of Severe Acute Respiratory Syndrome Coronavirus 3b Protein

  • Yuan, Xiaoling;Shan, Yajun;Yao, Zhenyu;Li, Jianyong;Zhao, Zhenhu;Chen, Jiapei;Cong, Yuwen
    • Molecules and Cells
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    • v.21 no.2
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    • pp.186-191
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    • 2006
  • Severe acute respiratory syndrome-associated coronavirus (SARS-CoV), a distant member of the Group 2 coronaviruses, has recently been identified as the etiological agent of severe acute respiratory syndrome (SARS). The genome of SARS-CoV contains four structural genes that are homologous to genes found in other coronaviruses, as well as six subgroup-specific open reading frames (ORFs). ORF3 encodes a predicted 154-amino-acid protein that lacks similarity to any known protein, and is designated 3b in this article. We reported previously that SARS-CoV 3b is predominantly localized in the nucleolus, and induces G0/G1 arrest and apoptosis in transfected cells. In this study, we show that SARS-CoV 3b fused with EGFP at its N- or C- terminus co-localized with a mitochondriaspecific marker in some transfected cells. Mutation analysis of SARS-CoV 3b revealed that the domain spanning amino acids 80 to 138 was essential for its mitochondria localization. These results provide new directions for studies of the role of SARS-CoV 3b protein in SARS pathogenesis.

Korean Red Ginseng, a regulator of NLRP3 inflammasome, in the COVID-19 pandemic

  • Jung, Eui-Man;Lee, Geun-Shik
    • Journal of Ginseng Research
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    • v.46 no.3
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    • pp.331-336
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    • 2022
  • Coronavirus disease 2019 (COVID-19) exhibits various symptoms, ranging from asymptomatic to severe pneumonia or death. The major features of patients in severe COVID-19 are the dysregulation of cytokine secretion, pneumonia, and acute lung injury. Consequently, it leads to acute respiratory distress syndrome, disseminated intravascular coagulation, multiple organ failure, and death. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of COVID-19, influences nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 (NLRP3), the sensor of inflammasomes, directly or indirectly, culminating in the assembly of NLRP3 inflammasome and activation of inflammatory caspases, which induce the inflammatory disruption in severe COVID-19. Accordingly, the target therapeutics for inflammasome has attracted attention as a treatment for COVID-19. Korean Red Ginseng (KRG) inhibits several inflammatory responses, including the NLRP3 inflammasome signaling. This review discusses the role of KRG in the treatment and prevention of COVID-19 based on its anti-NLRP3 inflammasome efficacy.

COVID-19 Antiviral and Treatment Candidates: Current Status

  • Erica Espano;Dajung Kim;Jiyeon Kim;Song-Kyu Park;Jeong-Ki Kim
    • IMMUNE NETWORK
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    • v.21 no.1
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    • pp.7.1-7.24
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    • 2021
  • The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 has severely impacted global health and economy. There is currently no effective approved treatment for COVID-19; although vaccines have been granted emergency use authorization in several countries, they are currently only administered to high-risk individuals, thereby leaving a gap in virus control measures. The scientific and clinical communities and drug manufacturers have collaborated to speed up the discovery of potential therapies for COVID-19 by taking advantage of currently approved drugs as well as investigatory agents in clinical trials. In this review, we stratified some of these candidates based on their potential targets in the progression of COVID-19 and discuss some of the results of ongoing clinical evaluations.

Nucleocapsid and Spike Proteins of SARS-CoV-2 Drive Neutrophil Extracellular Trap Formation

  • Young-Jin Youn;Yu-Bin Lee;Sun-Hwa Kim;Hee Kyung Jin;Jae-sung Bae;Chang-Won Hong
    • IMMUNE NETWORK
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    • v.21 no.2
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    • pp.16.1-16.8
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    • 2021
  • Patients with severe coronavirus disease 2019 (COVID-19) demonstrate dysregulated immune responses including exacerbated neutrophil functions. Massive neutrophil infiltrations accompanying neutrophil extracellular trap (NET) formations are also observed in patients with severe COVID-19. However, the mechanism underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced NET formation has not yet been elucidated. Here we show that 2 viral proteins encoded by SARS-CoV-2, the nucleocapsid protein and the whole spike protein, induce NET formation from neutrophils. NET formation was ROSindependent and was completely inhibited by the spleen tyrosine kinase inhibition. The inhibition of p38 MAPK, protein kinase C, and JNK signaling pathways also inhibited viral protein-induced NET formation. Our findings demonstrate one method by which SARSCoV-2 evades innate immunity and provide a potential target for therapeutics to treat patients with severe COVID-19.

Association among Lifestyle and Risk Factors with SARS-CoV-2 Infection

  • Yi Ko;Zi-Ni Ngai;Rhun-Yian Koh;Soi-Moi Chye
    • Tuberculosis and Respiratory Diseases
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    • v.86 no.2
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    • pp.102-110
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    • 2023
  • Coronavirus disease 2019 (COVID-19) has become a major health burden worldwide, with over 600 million confirmed cases and 6 million deaths by 15 December 2022. Although the acute phase of COVID-19 management has been established, the long-term clinical course and complications due to the relatively short outbreak is yet to be assessed. The current COVID-19 pandemic is causing significant morbidity and mortality around the world. Interestingly, epidemiological studies have shown that fatality rates vary considerably across different countries, and men and elderly patients are at higher risk of developing severe diseases. There is increasing evidence that COVID-19 infection causes neurological deficits in a substantial proportion to patients suffering from acute respiratory distress syndrome. Furthermore, lack of physical activity and smoking are associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) susceptibility. We should therefore explore why lack of physical activity, smoking, etc causing a population more susceptible to SARS-CoV-2 infection, and mechanism involved. Thus, in this review article, we summarize epidemiological evidence related to risk factors and lifestyle that affect COVID-19 severity and the mechanism involved. These risk factors or lifestyle interventions include smoking, cardiovascular health, obesity, exercise, environmental pollution, psychosocial social stress, and diet.

A Case of Isolated Acute Pancreatitis Presenting With Epigastric Pain in an 8-Year-Old Child Infected With COVID-19 (명치 통증으로 내원한 COVID-19에 감염된 8세 소아의 단독 급성 췌장염 1례)

  • Joo Ok Jin;Se Ri Jeong;Byung Ok Kwak;Sook Min Hwang;Ky Young Cho
    • Pediatric Infection and Vaccine
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    • v.30 no.2
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    • pp.104-110
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    • 2023
  • Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mainly causes respiratory symptoms such as fever, cough, sputum, and rhinorrhea, as well as digestive symptoms such as diarrhea, vomiting, and abdominal pain in children. In this report, we describe a case of a child with a SARS-CoV-2 infection who presented with epigastric pain and was subsequently diagnosed with acute pancreatitis without any concomitant infections in other organs. The epigastric pain was relieved with goal-directed vigorous fluid therapy for acute pancreatitis for 24 hours, and the serological and radiological findings normalized after two months. Acute pancreatitis should be considered as a differential diagnosis when a child with a history of COVID-19 visits the hospital with epigastric pain.

COVID-19 Therapeutics: An Update on Effective Treatments Against Infection With SARS-CoV-2 Variants

  • Bill Thaddeus Padasas;Erica Espano;Sang-Hyun Kim;Youngcheon Song;Chong-Kil Lee;Jeong-Ki Kim
    • IMMUNE NETWORK
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    • v.23 no.2
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    • pp.13.1-13.24
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    • 2023
  • The coronavirus disease 2019 (COVID-19) pandemic is one of the most consequential global health crises in over a century. Since its discovery in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to mutate into different variants and sublineages, rendering previously potent treatments and vaccines ineffective. With significant strides in clinical and pharmaceutical research, different therapeutic strategies continue to be developed. The currently available treatments can be broadly classified based on their potential targets and molecular mechanisms. Antiviral agents function by disrupting different stages of SARS-CoV-2 infection, while immune-based treatments mainly act on the human inflammatory response responsible for disease severity. In this review, we discuss some of the current treatments for COVID-19, their mode of actions, and their efficacy against variants of concern. This review highlights the need to constantly evaluate COVID-19 treatment strategies to protect high risk populations and fill in the gaps left by vaccination.