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1.
Am J Physiol Heart Circ Physiol ; 318(5): H1084-H1090, 2020 05 01.
Article in English | MEDLINE | ID: covidwho-707207

ABSTRACT

The novel SARS coronavirus SARS-CoV-2 pandemic may be particularly deleterious to patients with underlying cardiovascular disease (CVD). The mechanism for SARS-CoV-2 infection is the requisite binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. Recognition that ACE2 is the coreceptor for the coronavirus has prompted new therapeutic approaches to block the enzyme or reduce its expression to prevent the cellular entry and SARS-CoV-2 infection in tissues that express ACE2 including lung, heart, kidney, brain, and gut. ACE2, however, is a key enzymatic component of the renin-angiotensin-aldosterone system (RAAS); ACE2 degrades ANG II, a peptide with multiple actions that promote CVD, and generates Ang-(1-7), which antagonizes the effects of ANG II. Moreover, experimental evidence suggests that RAAS blockade by ACE inhibitors, ANG II type 1 receptor antagonists, and mineralocorticoid antagonists, as well as statins, enhance ACE2 which, in part, contributes to the benefit of these regimens. In lieu of the fact that many older patients with hypertension or other CVDs are routinely treated with RAAS blockers and statins, new clinical concerns have developed regarding whether these patients are at greater risk for SARS-CoV-2 infection, whether RAAS and statin therapy should be discontinued, and the potential consequences of RAAS blockade to COVID-19-related pathologies such as acute and chronic respiratory disease. The current perspective critically examines the evidence for ACE2 regulation by RAAS blockade and statins, the cardiovascular benefits of ACE2, and whether ACE2 blockade is a viable approach to attenuate COVID-19.


Subject(s)
Betacoronavirus/physiology , Cardiovascular Diseases/enzymology , Cardiovascular Diseases/virology , Coronavirus Infections/enzymology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/enzymology , Animals , Betacoronavirus/metabolism , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Humans , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Rats , Rats, Inbred Lew , Virus Internalization
2.
Physiol Rev ; 100(4): 1455-1466, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-706886

ABSTRACT

First isolated in China in early 2020, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for the ongoing pandemic of Coronavirus Disease 2019 (COVID-19). The disease has been spreading rapidly across the globe, with the largest burden falling on China, Europe, and the United States. COVID-19 is a new clinical syndrome, characterized by respiratory symptoms with varying degrees of severity, from mild upper respiratory illness to severe interstitial pneumonia and acute respiratory distress syndrome, aggravated by thrombosis in the pulmonary microcirculation. Three main phases of disease progression have been proposed for COVID-19: an early infection phase, a pulmonary phase, and a hyperinflammation phase. Although current understanding of COVID-19 treatment is mainly derived from small uncontrolled trials that are affected by a number of biases, strong background noise, and a litany of confounding factors, emerging awareness suggests that drugs currently used to treat COVID-19 (antiviral drugs, antimalarial drugs, immunomodulators, anticoagulants, and antibodies) should be evaluated in relation to the pathophysiology of disease progression. Drawing upon the dramatic experiences taking place in Italy and around the world, here we review the changes in the evolution of the disease and focus on current treatment uncertainties and promising new therapies.


Subject(s)
Betacoronavirus , Coronavirus Infections/pathology , Coronavirus Infections/virology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Antimalarials/therapeutic use , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Global Health , Humans , Immunologic Factors/therapeutic use , Pandemics , Pneumonia, Viral/drug therapy
4.
J Exp Med ; 217(11)2020 11 02.
Article in English | MEDLINE | ID: covidwho-697830

ABSTRACT

The emergence of SARS-CoV-2 and the ensuing explosive epidemic of COVID-19 disease has generated a need for assays to rapidly and conveniently measure the antiviral activity of SARS-CoV-2-specific antibodies. Here, we describe a collection of approaches based on SARS-CoV-2 spike-pseudotyped, single-cycle, replication-defective human immunodeficiency virus type-1 (HIV-1), and vesicular stomatitis virus (VSV), as well as a replication-competent VSV/SARS-CoV-2 chimeric virus. While each surrogate virus exhibited subtle differences in the sensitivity with which neutralizing activity was detected, the neutralizing activity of both convalescent plasma and human monoclonal antibodies measured using each virus correlated quantitatively with neutralizing activity measured using an authentic SARS-CoV-2 neutralization assay. The assays described herein are adaptable to high throughput and are useful tools in the evaluation of serologic immunity conferred by vaccination or prior SARS-CoV-2 infection, as well as the potency of convalescent plasma or human monoclonal antibodies.


Subject(s)
Antibodies, Neutralizing/analysis , Antibodies, Viral/analysis , Betacoronavirus/immunology , Coronavirus Infections/immunology , Immunoassay/methods , Pneumonia, Viral/immunology , Animals , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus/genetics , Cell Line , Chimera/genetics , Chimera/immunology , Chlorocebus aethiops , Coronavirus Infections/virology , HEK293 Cells , HIV-1/genetics , HIV-1/immunology , Humans , Neutralization Tests/methods , Pandemics , Pneumonia, Viral/virology , Recombination, Genetic , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vero Cells , Vesicular stomatitis Indiana virus/genetics , Vesicular stomatitis Indiana virus/immunology
5.
Radiology ; 296(2): E46-E54, 2020 08.
Article in English | MEDLINE | ID: covidwho-697192

ABSTRACT

Background Despite its high sensitivity in diagnosing coronavirus disease 2019 (COVID-19) in a screening population, the chest CT appearance of COVID-19 pneumonia is thought to be nonspecific. Purpose To assess the performance of radiologists in the United States and China in differentiating COVID-19 from viral pneumonia at chest CT. Materials and Methods In this study, 219 patients with positive COVID-19, as determined with reverse-transcription polymerase chain reaction (RT-PCR) and abnormal chest CT findings, were retrospectively identified from seven Chinese hospitals in Hunan Province, China, from January 6 to February 20, 2020. Two hundred five patients with positive respiratory pathogen panel results for viral pneumonia and CT findings consistent with or highly suspicious for pneumonia, according to original radiologic interpretation within 7 days of each other, were identified from Rhode Island Hospital in Providence, RI. Three radiologists from China reviewed all chest CT scans (n = 424) blinded to RT-PCR findings to differentiate COVID-19 from viral pneumonia. A sample of 58 age-matched patients was randomly selected and evaluated by four radiologists from the United States in a similar fashion. Different CT features were recorded and compared between the two groups. Results For all chest CT scans (n = 424), the accuracy of the three radiologists from China in differentiating COVID-19 from non-COVID-19 viral pneumonia was 83% (350 of 424), 80% (338 of 424), and 60% (255 of 424). In the randomly selected sample (n = 58), the sensitivities of three radiologists from China and four radiologists from the United States were 80%, 67%, 97%, 93%, 83%, 73%, and 70%, respectively. The corresponding specificities of the same readers were 100%, 93%, 7%, 100%, 93%, 93%, and 100%, respectively. Compared with non-COVID-19 pneumonia, COVID-19 pneumonia was more likely to have a peripheral distribution (80% vs 57%, P < .001), ground-glass opacity (91% vs 68%, P < .001), fine reticular opacity (56% vs 22%, P < .001), and vascular thickening (59% vs 22%, P < .001), but it was less likely to have a central and peripheral distribution (14% vs 35%, P < .001), pleural effusion (4% vs 39%, P < .001), or lymphadenopathy (3% vs 10%, P = .002). Conclusion Radiologists in China and in the United States distinguished coronavirus disease 2019 from viral pneumonia at chest CT with moderate to high accuracy. © RSNA, 2020 Online supplemental material is available for this article. A translation of this abstract in Farsi is available in the supplement. ترجمه چکیده این مقاله به فارسی، در ضمیمه موجود است.


Subject(s)
Betacoronavirus , Clinical Competence , Coronavirus Infections/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Radiologists/standards , Adult , Aged , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/pathology , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Predictive Value of Tests , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Tomography, X-Ray Computed/methods
6.
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
7.
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 Cell Biol ; 219(9)2020 09 07.
Article in English | MEDLINE | ID: covidwho-691118

ABSTRACT

Similar to other RNA viruses, SARS-CoV-2 must (1) enter a target/host cell, (2) reprogram it to ensure its replication, (3) exit the host cell, and (4) repeat this cycle for exponential growth. During the exit step, the virus hijacks the sophisticated machineries that host cells employ to correctly fold, assemble, and transport proteins along the exocytic pathway. Therefore, secretory pathway-mediated assemblage and excretion of infective particles represent appealing targets to reduce the efficacy of virus biogenesis, if not to block it completely. Here, we analyze and discuss the contribution of the molecular machines operating in the early secretory pathway in the biogenesis of SARS-CoV-2 and their relevance for potential antiviral targeting. The fact that these molecular machines are conserved throughout evolution, together with the redundancy and tissue specificity of their components, provides opportunities in the search for unique proteins essential for SARS-CoV-2 biology that could also be targeted with therapeutic objectives. Finally, we provide an overview of recent evidence implicating proteins of the early secretory pathway as potential antiviral targets with effective therapeutic applications.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/virology , Pneumonia, Viral/virology , Secretory Pathway/physiology , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Humans , Pandemics , Pneumonia, Viral/drug therapy , Secretory Pathway/drug effects , Virus Replication/drug effects , Virus Replication/physiology
10.
Euro Surveill ; 25(30)2020 07.
Article in English | MEDLINE | ID: covidwho-690919

ABSTRACT

We analysed consecutive RT-qPCR results of 537 symptomatic coronavirus disease (COVID-19) patients in home quarantine. Respectively 2, 3, and 4 weeks after symptom onset, 50%, 25% and 10% of patients had detectable RNA from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In patients with mild COVID-19, RNA detection is likely to outlast currently known periods of infectiousness by far and fixed time periods seem more appropriate in determining the length of home isolation than laboratory-based approaches.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Coronavirus/genetics , Pandemics , Pneumonia, Viral , RNA Replicase/genetics , Real-Time Polymerase Chain Reaction/methods , Viral Nonstructural Proteins/genetics , Adult , Aged , Aged, 80 and over , Betacoronavirus/isolation & purification , Coronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Germany/epidemiology , Humans , Middle Aged , Patient Isolation , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Quarantine , Survival Analysis , Time Factors
11.
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
12.
Elife ; 92020 07 30.
Article in English | MEDLINE | ID: covidwho-690669

ABSTRACT

The COVID-19 pandemic caused by the SARS-CoV-2 has recently emerged as a serious jolt to human life and economy. Initial knowledge established pulmonary complications as the chief symptom, however, the neurological aspect of the disease is also becoming increasingly evident. Emerging reports of encephalopathies and similar ailments with the detection of the virus in the CSF has elicited an urgent need for investigating the possibility of neuroinvasiveness of the virus, which cannot be ruled out given the expression of low levels of ACE2 receptors in the brain. Sensory impairments of the olfactory and gustatory systems have also been reported in a large proportion of the cases, indicating the involvement of the peripheral nervous system. Hence, the possibility of neurological damage caused by the virus demands immediate attention and investigation of the mechanisms involved, so as to customize the treatment of patients presenting with neurological complications.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Nervous System Diseases/etiology , Pneumonia, Viral/complications , Ageusia/etiology , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , Brain/metabolism , Brain/virology , Cerebrovascular Disorders/etiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Encephalitis, Viral/etiology , Host Microbial Interactions , Humans , Models, Neurological , Nervous System Diseases/physiopathology , Nervous System Diseases/virology , Olfaction Disorders/etiology , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Receptors, Virus/metabolism
13.
PLoS Med ; 17(7): e1003189, 2020 07.
Article in English | MEDLINE | ID: covidwho-690567

ABSTRACT

BACKGROUND: As of 16 May 2020, more than 4.5 million cases and more than 300,000 deaths from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. Reliable estimates of mortality from SARS-CoV-2 infection are essential for understanding clinical prognosis, planning healthcare capacity, and epidemic forecasting. The case-fatality ratio (CFR), calculated from total numbers of reported cases and reported deaths, is the most commonly reported metric, but it can be a misleading measure of overall mortality. The objectives of this study were to (1) simulate the transmission dynamics of SARS-CoV-2 using publicly available surveillance data and (2) infer estimates of SARS-CoV-2 mortality adjusted for biases and examine the CFR, the symptomatic case-fatality ratio (sCFR), and the infection-fatality ratio (IFR) in different geographic locations. METHOD AND FINDINGS: We developed an age-stratified susceptible-exposed-infected-removed (SEIR) compartmental model describing the dynamics of transmission and mortality during the SARS-CoV-2 epidemic. Our model accounts for two biases: preferential ascertainment of severe cases and right-censoring of mortality. We fitted the transmission model to surveillance data from Hubei Province, China, and applied the same model to six regions in Europe: Austria, Bavaria (Germany), Baden-Württemberg (Germany), Lombardy (Italy), Spain, and Switzerland. In Hubei, the baseline estimates were as follows: CFR 2.4% (95% credible interval [CrI] 2.1%-2.8%), sCFR 3.7% (3.2%-4.2%), and IFR 2.9% (2.4%-3.5%). Estimated measures of mortality changed over time. Across the six locations in Europe, estimates of CFR varied widely. Estimates of sCFR and IFR, adjusted for bias, were more similar to each other but still showed some degree of heterogeneity. Estimates of IFR ranged from 0.5% (95% CrI 0.4%-0.6%) in Switzerland to 1.4% (1.1%-1.6%) in Lombardy, Italy. In all locations, mortality increased with age. Among individuals 80 years or older, estimates of the IFR suggest that the proportion of all those infected with SARS-CoV-2 who will die ranges from 20% (95% CrI 16%-26%) in Switzerland to 34% (95% CrI 28%-40%) in Spain. A limitation of the model is that count data by date of onset are required, and these are not available in all countries. CONCLUSIONS: We propose a comprehensive solution to the estimation of SARS-Cov-2 mortality from surveillance data during outbreaks. The CFR is not a good predictor of overall mortality from SARS-CoV-2 and should not be used for evaluation of policy or comparison across settings. Geographic differences in IFR suggest that a single IFR should not be applied to all settings to estimate the total size of the SARS-CoV-2 epidemic in different countries. The sCFR and IFR, adjusted for right-censoring and preferential ascertainment of severe cases, are measures that can be used to improve and monitor clinical and public health strategies to reduce the deaths from SARS-CoV-2 infection.


Subject(s)
Coronavirus Infections/mortality , Pneumonia, Viral/mortality , Age Factors , Betacoronavirus/isolation & purification , China/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Europe/epidemiology , Humans , Models, Statistical , Pandemics , Pneumonia, Viral/transmission , Pneumonia, Viral/virology
14.
Sci Immunol ; 5(49)2020 07 29.
Article in English | MEDLINE | ID: covidwho-690482

ABSTRACT

Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important for determining SARS-CoV-2 exposures within both individuals and populations. We validated a SARS-CoV-2 spike receptor binding domain serological test using 834 pre-pandemic samples and 31 samples from COVID-19 recovered donors. We then completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate exposure to SARS-CoV-2 within the community.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Health Status Disparities , Pneumonia, Viral/epidemiology , Pregnancy Complications, Infectious/epidemiology , Adult , African Americans/statistics & numerical data , Antibodies, Viral/immunology , Betacoronavirus/immunology , Clinical Laboratory Techniques/methods , Clinical Laboratory Techniques/statistics & numerical data , Cohort Studies , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Coronavirus Infections/virology , Female , Hispanic Americans/statistics & numerical data , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Pandemics , Philadelphia/epidemiology , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , Protein Domains/immunology , Seroepidemiologic Studies , Spike Glycoprotein, Coronavirus/immunology , Young Adult
15.
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
16.
J Proteome Res ; 19(4): 1351-1360, 2020 04 03.
Article in English | MEDLINE | ID: covidwho-688546

ABSTRACT

As the infection of 2019-nCoV coronavirus is quickly developing into a global pneumonia epidemic, the careful analysis of its transmission and cellular mechanisms is sorely needed. In this Communication, we first analyzed two recent studies that concluded that snakes are the intermediate hosts of 2019-nCoV and that the 2019-nCoV spike protein insertions share a unique similarity to HIV-1. However, the reimplementation of the analyses, built on larger scale data sets using state-of-the-art bioinformatics methods and databases, presents clear evidence that rebuts these conclusions. Next, using metagenomic samples from Manis javanica, we assembled a draft genome of the 2019-nCoV-like coronavirus, which shows 73% coverage and 91% sequence identity to the 2019-nCoV genome. In particular, the alignments of the spike surface glycoprotein receptor binding domain revealed four times more variations in the bat coronavirus RaTG13 than in the Manis coronavirus compared with 2019-nCoV, suggesting the pangolin as a missing link in the transmission of 2019-nCoV from bats to human.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/virology , Genome, Viral/genetics , Host-Pathogen Interactions , Models, Molecular , Pneumonia, Viral/virology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Amino Acid Sequence , Animals , Betacoronavirus/classification , Eutheria/virology , HIV-1/genetics , Humans , Metagenome , Pandemics , Protein Structure, Tertiary , Sequence Alignment , Sequence Analysis, Protein , Snakes/virology
17.
Neurologia ; 35(5): 318-322, 2020 Jun.
Article in English, Spanish | MEDLINE | ID: covidwho-688165

ABSTRACT

INTRODUCTION: Contradictory data have been reported on the incidence of stroke in patients with COVID-19 and the risk of SARS-CoV-2 infection among patients with history of stroke. METHODS: This study systematically reviews case series reporting stroke as a complication of COVID-19, and analyses the prognosis of patients with COVID-19 and history of stroke. The pathophysiological mechanisms of stroke in patients with COVID-19 are also reviewed. CONCLUSIONS: History of stroke increases the risk of death due to COVID-19 by 3 times. Stroke currently seems not to be one of the main complications of COVID-19.


Subject(s)
Central Nervous System Viral Diseases/pathology , Central Nervous System Viral Diseases/virology , Central Nervous System/virology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Stroke/virology , Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Humans , Pandemics , Pneumonia, Viral/virology , Prognosis
18.
Eur Rev Med Pharmacol Sci ; 24(9): 5186-5188, 2020 05.
Article in English | MEDLINE | ID: covidwho-687446

ABSTRACT

From two COVID-19-related deaths, samples of lung, heart and kidney were collected and processed for Transmission and Scanning Electron Microscopy (TEM and SEM) with the aim of identifying the virus. Virions of SARS-CoV-2 were found in all tissues by TEM and SEM, corroborating the hypothesis that the virus enters the cells of different organs. This is the first report identifying SARS-CoV-2 in different human tissues by TEM and SEM.


Subject(s)
Betacoronavirus/isolation & purification , Betacoronavirus/ultrastructure , Coronavirus Infections/virology , Heart/virology , Kidney/virology , Lung/virology , Pneumonia, Viral/virology , Aged , Aged, 80 and over , Coronavirus Infections/pathology , Female , Humans , Kidney/pathology , Lung/pathology , Male , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Pandemics , Pneumonia, Viral/pathology
19.
J Med Virol ; 92(6): 584-588, 2020 06.
Article in English | MEDLINE | ID: covidwho-685102

ABSTRACT

Last December 2019, a new virus, named novel Coronavirus (COVID-2019) causing many cases of severe pneumonia was reported in Wuhan, China. The virus knowledge is limited and especially about COVID-2019 pathogenesis. The Open Reading Frame 1ab (ORF1ab) of COVID-2019 has been analyzed to evidence the presence of mutation caused by selective pressure on the virus. For selective pressure analysis fast-unconstrained Bayesian approximation (FUBAR) was used. Homology modelling has been performed by SwissModel and HHPred servers. The presence of transmembrane helical segments in Coronavirus ORF1ab non structural protein 2 (nsp2) and nsp3 was tested by TMHMM, MEMSAT, and MEMPACK tools. Three-dimensional structures have been analyzed and displayed using PyMOL. FUBAR analysis revealed the presence of potential sites under positive selective pressure (P < .05). Position 723 in the COVID-2019 has a serine instead a glycine residue, while at aminoacidic position 1010 a proline instead an isoleucine. Significant (P < .05) pervasive negative selection in 2416 sites (55%) was found. The positive selective pressure could account for some clinical features of this virus compared with severe acute respiratory syndrome (SARS) and Bat SARS-like CoV. The stabilizing mutation falling in the endosome-associated-protein-like domain of the nsp2 protein could account for COVID-2019 high ability of contagious, while the destabilizing mutation in nsp3 proteins could suggest a potential mechanism differentiating COVID-2019 from SARS. These data could be helpful for further investigation aimed to identify potential therapeutic targets or vaccine strategy, especially in the actual moment when the epidemic is ongoing and the scientific community is trying to enrich knowledge about this new viral pathogen.


Subject(s)
Betacoronavirus/genetics , SARS Virus/genetics , Viral Nonstructural Proteins/chemistry , Viral Proteins/chemistry , Betacoronavirus/pathogenicity , Coronavirus Infections/virology , Female , Gene Expression , Humans , Male , Models, Molecular , Mutation , Pandemics , Pneumonia, Viral/virology , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , SARS Virus/pathogenicity , Selection, Genetic , Structural Homology, Protein , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/metabolism , Viral Proteins/genetics , Viral Proteins/metabolism
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