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1.
Scientific reports ; 12(1), 2022.
Article in English | EuropePMC | ID: covidwho-1651354

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus, responsible for outbreaks of a severe respiratory illness in humans with a fatality rate of 30%. Currently, there are no vaccines or United States food and drug administration (FDA)-approved therapeutics for humans. The spike protein displayed on the surface of MERS-CoV functions in the attachment and fusion of virions to host cellular membranes and is the target of the host antibody response. Here, we provide a molecular method for neutralizing MERS-CoV through potent antibody-mediated targeting of the receptor-binding subdomain (RBD) of the spike protein. The structural characterization of the neutralizing antibody (KNIH90-F1) complexed with RBD using X-ray crystallography revealed three critical epitopes (D509, R511, and E513) in the RBD region of the spike protein. Further investigation of MERS-CoV mutants that escaped neutralization by the antibody supported the identification of these epitopes in the RBD region. The neutralizing activity of this antibody is solely provided by these specific molecular structures. This work should contribute to the development of vaccines or therapeutic antibodies for MERS-CoV.

2.
Sci Rep ; 12(1): 1260, 2022 01 24.
Article in English | MEDLINE | ID: covidwho-1648095

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus, responsible for outbreaks of a severe respiratory illness in humans with a fatality rate of 30%. Currently, there are no vaccines or United States food and drug administration (FDA)-approved therapeutics for humans. The spike protein displayed on the surface of MERS-CoV functions in the attachment and fusion of virions to host cellular membranes and is the target of the host antibody response. Here, we provide a molecular method for neutralizing MERS-CoV through potent antibody-mediated targeting of the receptor-binding subdomain (RBD) of the spike protein. The structural characterization of the neutralizing antibody (KNIH90-F1) complexed with RBD using X-ray crystallography revealed three critical epitopes (D509, R511, and E513) in the RBD region of the spike protein. Further investigation of MERS-CoV mutants that escaped neutralization by the antibody supported the identification of these epitopes in the RBD region. The neutralizing activity of this antibody is solely provided by these specific molecular structures. This work should contribute to the development of vaccines or therapeutic antibodies for MERS-CoV.


Subject(s)
Antibodies, Monoclonal/chemistry , Antibodies, Neutralizing/chemistry , Antibodies, Viral/chemistry , Middle East Respiratory Syndrome Coronavirus/chemistry , Crystallography, X-Ray , Humans , Protein Domains
3.
Nature ; 599(7884): 283-289, 2021 11.
Article in English | MEDLINE | ID: covidwho-1404888

ABSTRACT

Derailed cytokine and immune cell networks account for the organ damage and the clinical severity of COVID-19 (refs. 1-4). Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and is accompanied by a senescence-associated secretory phenotype (SASP), which comprises pro-inflammatory cytokines, extracellular-matrix-active factors and pro-coagulatory mediators5-7. Patients with COVID-19 displayed markers of senescence in their airway mucosa in situ and increased serum levels of SASP factors. In vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, which mirrored hallmark features of COVID-19 such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue1,8,9. Moreover, supernatant from VIS cells, including SARS-CoV-2-induced senescence, induced neutrophil extracellular trap formation and activation of platelets and the clotting cascade. Senolytics such as navitoclax and a combination of dasatinib plus quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-infected hamsters and mice. Our findings mark VIS as a pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest that senolytic targeting of virus-infected cells is a treatment option against SARS-CoV-2 and perhaps other viral infections.


Subject(s)
COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Cellular Senescence/drug effects , Molecular Targeted Therapy , SARS-CoV-2/pathogenicity , Aniline Compounds/pharmacology , Aniline Compounds/therapeutic use , Animals , COVID-19/complications , Cell Line , Cricetinae , Dasatinib/pharmacology , Dasatinib/therapeutic use , Disease Models, Animal , Female , Humans , Male , Mice , Quercetin/pharmacology , Quercetin/therapeutic use , SARS-CoV-2/drug effects , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Thrombosis/complications , Thrombosis/immunology , Thrombosis/metabolism
5.
Sustainability ; 12(18), 2020.
Article in English | CAB Abstracts | ID: covidwho-1229290

ABSTRACT

This study investigated how social support influences the job engagement and job retention intention of nurses struggling in the continuing scenes of the COVID-19 pandemic. To this end, 382 nurses were the participants, data from 377 of whom were analyzed in total, with the following results. First, it showed that nurses' job engagement and job retention intention were high, depending on their age and work experience. Second, in terms of the factors related to COVID-19, the group with experience in nursing patients infected with COVID-19 and nurses working in COVID-19 divisions had low job retention intention. Lastly, it appeared that there were differences in job engagement and job retention intention depending on the category and type of social support. These results suggest that social support should be provided strategically to ensure nurses' job retention.

6.
J Clin Nurs ; 30(13-14): 1990-2000, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1146727

ABSTRACT

AIMS AND OBJECTIVES: This study aimed to compare anxiety, resilience, and depression between COVID-19 unit (confirmed patients and suspected patients) and non-COVID-19 unit nurses and assess their effects on depression. BACKGROUND: Nurses working during the global pandemic are known to be physically and psychologically exhausted, and experience severe anxiety and depression. However, there is a lack of studies comparing anxiety and depression between COVID-19 and non-COVID-19 unit nurses. DESIGN: Descriptive research study. METHODS: This study was conducted on 64 nurses who directly worked for more than a month in a COVID-19 unit of a general hospital with nationally designated negative-pressure isolation beds and 64 nurses working in a non-COVID-19 unit. Data were collected through questionnaires and were analysed using SPSS 25.0. Reporting of this research adheres to the STROBE guidelines. RESULTS: Anxiety and depression were significantly higher in nurses working with patients suspected to have COVID-19 rather than nurses working with confirmed COVID-19 patients and non-COVID-19 patients. Resilience was significantly lower in suspected patient unit nurses than in COVID-19 unit nurses. Anxiety was the major factor predicting depression in both COVID-19 unit (confirmed patients and suspected patients) and non-COVID-19 unit nurses with 76.6%, 80.7%, and 63.6% explanatory power, respectively. CONCLUSIONS: Among nurses working in COVID-19 units, suspected patients unit nurses had higher depression than confirmed patients unit nurses due to an unsafe facility environment, insufficient personal protective equipment, and unknown conditions of the patients. Thus, interventions which have a high impact on depression need to be provided to relieve anxiety. RELEVANCE TO CLINICAL PRACTICE: The nursing organisation must provide comprehensive support including coordinated shifts, internal motivation, incentives, up-to-date information, and clear infection prevention guidelines to relieve anxiety caused by exhaustive workload, uncertainty of infectious diseases, and lack of human and material resources.


Subject(s)
Anxiety/epidemiology , COVID-19/psychology , Depression/epidemiology , Nurses/psychology , Resilience, Psychological , Hospitals , Humans
7.
Phytother Res ; 34(12): 3200-3210, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-964631

ABSTRACT

Rosa rugosa Thunb., is as a medicinal plant known for anti-diabetic, and anti-inflammatory activities. However, the specific active compounds responsible for the individual pharmacological effects of in R. rugosa extract (95% EtOH) remain unknown. Here, we hypothesized that terpenoid structure, the most abundant constituents in R. rugosa extract, are responsible for its anti-inflammatory activity. We investigated the phytochemical substituents (compounds 1-13) and newly purified 11-methoxy polisin A, and 13-methoxy bisaborosaol F using NMR and ESI-MS and to screened their effects on NO production in LPS-induced macrophages. Rugosic acid A (RA) induced to ameliorate NO production, iNOS, and pro-inflammatory cytokines associated with the NF-κB. And, RA suppressed IL-6 secretion and IL-6-mediated STAT3 activation in LPS-mediated inflammation. In addition, RA was evaluated in LPS-mediated acute lung injury (ALI) model similar to acute pneumonia. Our results suggested that RA was suppressed to translocate nuclear NF-κB and IL-6-mediated STAT3 activation. Finally, RA led to amelioration of ALI by decreasing myeloperoxidase (MPO) and inhibiting phosphorylation of NF-κB and STAT3. Our group originally found that R. rugosa extract had new methoxy compounds and RA may be alternative natural agent for acute pneumonia similar to severe acute respiratory syndrome by coronavirus.


Subject(s)
Acute Lung Injury/drug therapy , Anti-Inflammatory Agents/therapeutic use , Interleukin-6/antagonists & inhibitors , NF-kappa B/antagonists & inhibitors , Rosa , STAT3 Transcription Factor/antagonists & inhibitors , Acute Lung Injury/chemically induced , Acute Lung Injury/immunology , Animals , Anti-Inflammatory Agents/pharmacology , Cell Line , Disease Models, Animal , Female , Humans , Lipopolysaccharides , Mice, Inbred BALB C
8.
Sustainability ; 12(18):7276, 2020.
Article | MDPI | ID: covidwho-762666

ABSTRACT

This study investigated how social support influences the job engagement and job retention intention of nurses struggling in the continuing scenes of the COVID-19 pandemic. To this end, 382 nurses were the participants, data from 377 of whom were analyzed in total, with the following results. First, it showed that nurses"job engagement and job retention intention were high, depending on their age and work experience. Second, in terms of the factors related to COVID-19, the group with experience in nursing patients infected with COVID-19 and nurses working in COVID-19 divisions had low job retention intention. Lastly, it appeared that there were differences in job engagement and job retention intention depending on the category and type of social support. These results suggest that social support should be provided strategically to ensure nurses"job retention.

9.
PLoS One ; 15(5): e0232757, 2020.
Article in English | MEDLINE | ID: covidwho-209798

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infection and continues to infect humans, thereby contributing to a high mortality rate (34.3% in 2019). In the absence of an available licensed vaccine and antiviral agent, therapeutic human antibodies have been suggested as candidates for treatment. In this study, human monoclonal antibodies were isolated by sorting B cells from patient's PBMC cells with prefusion stabilized spike (S) probes and a direct immunoglobulin cloning strategy. We identified six receptor-binding domain (RBD)-specific and five S1 (non-RBD)-specific antibodies, among which, only the RBD-specific antibodies showed high neutralizing potency (IC50 0.006-1.787 µg/ml) as well as high affinity to RBD. Notably, passive immunization using a highly potent antibody (KNIH90-F1) at a relatively low dose (2 mg/kg) completely protected transgenic mice expressing human DPP4 against MERS-CoV lethal challenge. These results suggested that human monoclonal antibodies isolated by using the rationally designed prefusion MERS-CoV S probe could be considered potential candidates for the development of therapeutic and/or prophylactic antiviral agents for MERS-CoV human infection.


Subject(s)
Antibodies, Monoclonal/pharmacology , Antibodies, Viral/pharmacology , Coronavirus Infections/drug therapy , Middle East Respiratory Syndrome Coronavirus/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/immunology , Antiviral Agents/pharmacology , Cell Line , Chlorocebus aethiops , Dipeptidyl Peptidase 4/genetics , Humans , Leukocytes, Mononuclear/immunology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Republic of Korea , Vero Cells
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