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1.
Biochem Biophys Res Commun ; 529(2): 251-256, 2020 08 20.
Article in English | MEDLINE | ID: covidwho-692859

ABSTRACT

The nucleocapsid protein is significant in the formation of viral RNA of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accounting for the largest proportion of viral structural proteins. Here, we report for the first time that the 11S proteasomal activator PA28γ regulates the intracellular abundance of the SARS-CoV-2 N protein (nCoV N). Furthermore, we have identified proteasome activator PA28γ as a nCoV N binding protein by co-immunoprecipitation assay. As a result of their interaction, nCoV N could be degraded by PA28γ-20S in vitro degradation assay. This was also demonstrated by blocking de novo protein synthesis with cycloheximide. The stability of nCoV N in PA28γ-knockout cells was greater than in PA28γ-wildtype cells. Notably, immunofluorescence staining revealed that knockout of the PA28γ gene in cells led to the transport of nCoV N from the nucleus to the cytoplasm. Overexpression of PA28γ enhanced proteolysis of nCoV N compared to that in PA28γ-N151Y cells containing a dominant-negative PA28γ mutation, which reduced this process. These results suggest that PA28γ binding is important in regulating 20S proteasome activity, which in turn regulates levels of the critical nCoV N nucleocapsid protein of SARS-CoV-2, furthering our understanding of the pathogenesis of COVID-19.


Subject(s)
Autoantigens/metabolism , Betacoronavirus/metabolism , Coronavirus Infections/metabolism , Nucleocapsid Proteins/metabolism , Pneumonia, Viral/metabolism , Proteasome Endopeptidase Complex/metabolism , Proteolysis , Coronavirus Infections/virology , HEK293 Cells , Humans , In Vitro Techniques , Pandemics , Pneumonia, Viral/virology , Protein Binding , Protein Stability , Protein Transport
2.
Int J Mol Sci ; 21(12)2020 Jun 26.
Article in English | MEDLINE | ID: covidwho-692289

ABSTRACT

In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of coronaviruses in the aftermath of the 2002-2003 severe acute respiratory syndrome (SARS) and 2012 Middle East respiratory syndrome (MERS) outbreaks. Furthermore, genome sequencing and bioinformatic analysis have had an unprecedented relevance in the battle against the 2019-2020 coronavirus disease 2019 (COVID-19) pandemic, the newest and most devastating outbreak caused by a coronavirus in the history of mankind. Here, we review how genomic information has been used to tackle outbreaks caused by emerging, highly pathogenic, betacoronavirus strains, emphasizing on SARS-CoV, MERS-CoV and SARS-CoV-2. We focus on shared genomic features of the betacoronaviruses and the application of genomic information to phylogenetic analysis, molecular epidemiology and the design of diagnostic systems, potential drugs and vaccine candidates.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/virology , Genome, Viral , Pandemics/prevention & control , Pneumonia, Viral/virology , Animals , Betacoronavirus/immunology , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Drug Design , Genes, Viral , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Molecular Epidemiology , Phylogeny , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , SARS Virus/genetics , Severe Acute Respiratory Syndrome/virology , Viral Vaccines/genetics , Viral Vaccines/immunology
8.
J Virol ; 94(15)2020 07 16.
Article in English | MEDLINE | ID: covidwho-690841

ABSTRACT

Currently, there are four seasonal coronaviruses associated with relatively mild respiratory tract disease in humans. However, there is also a plethora of animal coronaviruses which have the potential to cross the species border. This regularly results in the emergence of new viruses in humans. In 2002, severe acute respiratory syndrome coronavirus (SARS-CoV) emerged and rapidly disappeared in May 2003. In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a possible threat to humans, but its pandemic potential so far is minimal, as human-to-human transmission is ineffective. The end of 2019 brought us information about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emergence, and the virus rapidly spread in 2020, causing an unprecedented pandemic. At present, studies on the virus are carried out using a surrogate system based on the immortalized simian Vero E6 cell line. This model is convenient for diagnostics, but it has serious limitations and does not allow for understanding of the biology and evolution of the virus. Here, we show that fully differentiated human airway epithelium cultures constitute an excellent model to study infection with the novel human coronavirus SARS-CoV-2. We observed efficient replication of the virus in the tissue, with maximal replication at 2 days postinfection. The virus replicated in ciliated cells and was released apically.IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged by the end of 2019 and rapidly spread in 2020. At present, it is of utmost importance to understand the biology of the virus, rapidly assess the treatment potential of existing drugs, and develop new active compounds. While some animal models for such studies are under development, most of the research is carried out in Vero E6 cells. Here, we propose fully differentiated human airway epithelium cultures as a model for studies on SARS-CoV-2.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/virology , Pneumonia, Viral/virology , Respiratory Mucosa/virology , Severe Acute Respiratory Syndrome/virology , Virus Replication , Animals , Cell Line , Cells, Cultured , Chlorocebus aethiops , Humans , Pandemics , Vero Cells
10.
JMIR Public Health Surveill ; 6(3): e20737, 2020 07 21.
Article in English | MEDLINE | ID: covidwho-690354

ABSTRACT

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, social media platforms have become active sites for the dissemination of conspiracy theories that provide alternative explanations of the cause of the pandemic, such as secret plots by powerful and malicious groups. However, the association of individuals' beliefs in conspiracy theories about COVID-19 with mental health and well-being issues has not been investigated. This association creates an assessable channel to identify and provide assistance to people with mental health and well-being issues during the pandemic. OBJECTIVE: Our aim was to provide the first evidence that belief in conspiracy theories regarding the COVID-19 pandemic is a predictor of the mental health and well-being of health care workers. METHODS: We conducted a survey of 252 health care workers in Ecuador from April 10 to May 2, 2020. We analyzed the data regarding distress and anxiety caseness with logistic regression and the data regarding life and job satisfaction with linear regression. RESULTS: Among the 252 sampled health care workers in Ecuador, 61 (24.2%) believed that the virus was developed intentionally in a lab; 82 (32.5%) experienced psychological distress, and 71 (28.2%) had anxiety disorder. Compared to health care workers who were not sure where the virus originated, those who believed the virus was developed intentionally in a lab were more likely to report psychological distress and anxiety disorder and to have lower levels of job satisfaction and life satisfaction. CONCLUSIONS: This paper identifies belief in COVID-19 conspiracy theories as an important predictor of distress, anxiety, and job and life satisfaction among health care workers. This finding will enable mental health services to better target and provide help to mentally vulnerable health care workers during the ongoing COVID-19 pandemic.


Subject(s)
Coronavirus Infections , Coronavirus , Pandemics , Pneumonia, Viral , Betacoronavirus , Cross-Sectional Studies , Ecuador , Health Personnel , Humans , Mental Health , Surveys and Questionnaires
14.
Eur J Phys Rehabil Med ; 56(3): 335-338, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-689752

ABSTRACT

Corona virus disease 2019 (COVID-19) is a new disease characterized by lung damage and involvement in multiple tissues and organs in the whole body. Some of the patients may have long-term impairment and dysfunctions, including pulmonary fibrosis, heart, liver, kidney, nerve and immune system. Rehabilitation has certain beneficial effect in the acute stage, and especially in the recovery stage, including improving respiratory function, exercise endurance, self-care in daily living activities, as well as psychological support, etc. Rehabilitation is not offside or absent. A reasonable rehabilitation program needs scientific research to avoid arbitrary conclusions.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/rehabilitation , Pneumonia, Viral/complications , Pneumonia, Viral/rehabilitation , Activities of Daily Living , China/epidemiology , Coronavirus Infections/epidemiology , Exercise Therapy , Humans , Pandemics , Pneumonia, Viral/epidemiology
16.
Lancet Respir Med ; 8(7): e63-e64, 2020 07.
Article in English | MEDLINE | ID: covidwho-689472
17.
Med Sci Monit ; 26: e925047, 2020 Jul 28.
Article in English | MEDLINE | ID: covidwho-689085

ABSTRACT

BACKGROUND The aim of this study was to describe the clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and compare these parameters in an elderly group with those in a younger group. MATERIAL AND METHODS This retrospective, single-center observational study included 69 hospitalized patients with laboratory-confirmed COVID-19 from a tertiary hospital in Wuhan, China, between January 14, 2020, and February 26, 2020. Epidemiological, demographic, clinical, and laboratory data, as well as treatments, complications, and outcomes were extracted from electronic medical records and compared between elderly patients (aged ≥60 years) and younger patients (aged <60 years). Patients were followed until March 19, 2020. RESULTS Elderly patients had more complications than younger patients, including acute respiratory distress syndrome (ARDS; 9/25, 36% vs. 5/44, 11.4%) and cardiac injury (7/25, 28% vs. 1/44, 2.3%), and they were more likely to be admitted to the intensive care unit (6/25, 24% vs. 2/44, 4.5%). As of March 19, 2020, 60/69 (87%) of the patients had been discharged, 6/69 (8.7%) had died, and 3/69 (4.3%) remained in the hospital. Of those who were discharged or died, the median duration of hospitalization was 13.5 days (interquartile range, 10-18 days). CONCLUSIONS Elderly patients with confirmed COVID-19 were more likely to develop ARDS and cardiac injury than younger patients and were more likely to be admitted to the intensive care unit. In addition to routine monitoring and respiratory support, cardiac monitoring and supportive care should be a focus in elderly patients with COVID-19.


Subject(s)
Age Factors , Coronavirus Infections/epidemiology , Heart Diseases/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Respiratory Distress Syndrome, Adult/epidemiology , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Adult , Aged , Aged, 80 and over , Betacoronavirus , China/epidemiology , Combined Modality Therapy , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , Heart Diseases/etiology , Humans , Inpatients , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Male , Middle Aged , Multiple Organ Failure/epidemiology , Multiple Organ Failure/etiology , Palliative Care/statistics & numerical data , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Respiratory Distress Syndrome, Adult/etiology , Retrospective Studies , Tertiary Care Centers , Treatment Outcome , Young Adult
18.
Kardiologiia ; 60(6): 1180, 2020 May 25.
Article in Russian | MEDLINE | ID: covidwho-689072

ABSTRACT

This article discusses relevant aspects in the treatment of patients with COVID-19. Up-to-date information about principles for administration of statins, antithrombotics, and antiarrhythmics is presented. The authors addressed in detail specific features of reversing heart rhythm disorders in patients with coronavirus infection and the interaction of antiarrhythmic and antiviral drugs. Recommendations are provided for outpatient and inpatient antithrombotic therapy for patients with COVID-19. Issues of antithrombotic and antiviral drug interaction are discussed.


Subject(s)
Anticoagulants , Cardiology , Coronavirus Infections , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Pandemics , Pneumonia, Viral , Anti-Arrhythmia Agents/therapeutic use , Anticoagulants/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Russia , Societies, Medical
20.
Postepy Biochem ; 66(2): 83-90, 2020 05 09.
Article in Polish | MEDLINE | ID: covidwho-689005

ABSTRACT

In December 2019 in Wuhan, China the first cases of previously unknown, coronaviral infection-induced pneumonia have been reported. The new virus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) was named after SARS-CoV due to their similarities and the disease caused by the pathogen is COVID-19 (Coronavirus Disease 2019). On 11 March 2020 WHO (World Health Organization) defined the rapidly increasing number of incidents of COVID-19 as a pandemic. In this review we will present recent information about the SARS-CoV-2 focusing on the origin, clinical picture, diagnostic methods, structure, replication cycle of SARS-CoV-2 and potential pharmaceutical measures against COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Betacoronavirus/growth & development , Betacoronavirus/isolation & purification , Betacoronavirus/pathogenicity , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Humans , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , SARS Virus
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