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1.
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
2.
Front Immunol ; 11: 1581, 2020.
Article in English | MEDLINE | ID: covidwho-688990

ABSTRACT

To ultimately combat the emerging COVID-19 pandemic, it is desired to develop an effective and safe vaccine against this highly contagious disease caused by the SARS-CoV-2 coronavirus. Our literature and clinical trial survey showed that the whole virus, as well as the spike (S) protein, nucleocapsid (N) protein, and membrane (M) protein, have been tested for vaccine development against SARS and MERS. However, these vaccine candidates might lack the induction of complete protection and have safety concerns. We then applied the Vaxign and the newly developed machine learning-based Vaxign-ML reverse vaccinology tools to predict COVID-19 vaccine candidates. Our Vaxign analysis found that the SARS-CoV-2 N protein sequence is conserved with SARS-CoV and MERS-CoV but not from the other four human coronaviruses causing mild symptoms. By investigating the entire proteome of SARS-CoV-2, six proteins, including the S protein and five non-structural proteins (nsp3, 3CL-pro, and nsp8-10), were predicted to be adhesins, which are crucial to the viral adhering and host invasion. The S, nsp3, and nsp8 proteins were also predicted by Vaxign-ML to induce high protective antigenicity. Besides the commonly used S protein, the nsp3 protein has not been tested in any coronavirus vaccine studies and was selected for further investigation. The nsp3 was found to be more conserved among SARS-CoV-2, SARS-CoV, and MERS-CoV than among 15 coronaviruses infecting human and other animals. The protein was also predicted to contain promiscuous MHC-I and MHC-II T-cell epitopes, and the predicted linear B-cell epitopes were found to be localized on the surface of the protein. Our predicted vaccine targets have the potential for effective and safe COVID-19 vaccine development. We also propose that an "Sp/Nsp cocktail vaccine" containing a structural protein(s) (Sp) and a non-structural protein(s) (Nsp) would stimulate effective complementary immune responses.


Subject(s)
Betacoronavirus , Coronavirus Infections , Machine Learning , Pandemics , Pneumonia, Viral , Viral Vaccines , Animals , Betacoronavirus/genetics , Betacoronavirus/immunology , Coronavirus Infections/epidemiology , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Epitopes, B-Lymphocyte/genetics , Epitopes, B-Lymphocyte/immunology , Humans , Immunogenicity, Vaccine , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/immunology , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/genetics , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Viral Proteins/genetics , Viral Proteins/immunology , Viral Vaccines/genetics , Viral Vaccines/immunology
3.
Infect Dis Poverty ; 9(1): 99, 2020 Jul 20.
Article in English | MEDLINE | ID: covidwho-655343

ABSTRACT

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has caused a public catastrophe and global concern. The main symptoms of COVID-19 are fever, cough, myalgia, fatigue and lower respiratory tract infection signs. Almost all populations are susceptible to the virus, and the basic reproduction number (R0) is 2.8-3.9. The fight against COVID-19 should have two aspects: one is the treatment of infected patients, and the other is the mobilization of the society to avoid the spread of the virus. The treatment of patients includes supportive treatment, antiviral treatment, and oxygen therapy. For patients with severe acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) and circulatory support are recommended. Plasma therapy and traditional Chinese medicine have also achieved good outcomes. This review is intended to summarize the research on this new coronavirus, to analyze the similarities and differences between COVID-19 and previous outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and to provide guidance regarding new methods of prevention, diagnosis and clinical treatment based on autodock simulations. METHODS: This review compares the multifaceted characteristics of the three coronaviruses including COVID-19, SARS and MERS. Our researchers take the COVID-19, SARS, and MERS as key words and search literatures in the Pubmed database. We compare them horizontally and vertically which respectively means concluding the individual characteristics of each coronavirus and comparing the similarities and differences between the three coronaviruses. RESULTS: We searched for studies on each outbreak and their solutions and found that the main biological differences among SARS-CoV-2, SARS-CoV and MERS-CoV are in ORF1a and the sequence of gene spike coding protein-S. We also found that the types and severity of clinical symptoms vary, which means that the diagnosis and nursing measures also require differentiation. In addition to the common route of transmission including airborne transmission, these three viruses have their own unique routes of transmission such as fecal-oral route of transmission COVID-19. CONCLUSIONS: In evolutionary history, these three coronaviruses have some similar biological features as well as some different mutational characteristics. Their receptors and routes of transmission are not all the same, which makes them different in clinical features and treatments. We discovered through the autodock simulations that Met124 plays a key role in the efficiency of drugs targeting ACE2, such as remdesivir, chloroquine, ciclesonide and niclosamide, and may be a potential target in COVID-19.


Subject(s)
Antiviral Agents/chemistry , Coronavirus Infections , Pandemics , Peptidyl-Dipeptidase A/chemistry , Pneumonia, Viral , Receptors, Virus/chemistry , Severe Acute Respiratory Syndrome , Animals , Antiviral Agents/metabolism , Betacoronavirus/genetics , Betacoronavirus/physiology , Betacoronavirus/ultrastructure , Clinical Laboratory Techniques , Clinical Trials as Topic , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Disease Reservoirs , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/physiology , Middle East Respiratory Syndrome Coronavirus/ultrastructure , Molecular Docking Simulation , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission , Receptors, Virus/metabolism , SARS Virus/genetics , SARS Virus/physiology , SARS Virus/ultrastructure , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/transmission
4.
Nature ; 583(7816): 360, 2020 07.
Article in English | MEDLINE | ID: covidwho-647057
6.
Immunol Rev ; 296(1): 205-219, 2020 07.
Article in English | MEDLINE | ID: covidwho-641222

ABSTRACT

This article provides a review of studies evaluating the role of host (and viral) genetics (including variation in HLA genes) in the immune response to coronaviruses, as well as the clinical outcome of coronavirus-mediated disease. The initial sections focus on seasonal coronaviruses, SARS-CoV, and MERS-CoV. We then examine the state of the knowledge regarding genetic polymorphisms and SARS-CoV-2 and COVID-19. The article concludes by discussing research areas with current knowledge gaps and proposes several avenues for future scientific exploration in order to develop new insights into the immunology of SARS-CoV-2.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Disease Resistance/genetics , Genetic Predisposition to Disease , Host-Pathogen Interactions/genetics , Pneumonia, Viral/immunology , Animals , Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Coronavirus Infections/genetics , Coronavirus Infections/virology , Host-Pathogen Interactions/immunology , Humans , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/genetics , Pneumonia, Viral/virology , SARS Virus/immunology , SARS Virus/pathogenicity , Severe Acute Respiratory Syndrome/genetics , Severe Acute Respiratory Syndrome/virology
7.
PLoS One ; 15(7): e0235653, 2020.
Article in English | MEDLINE | ID: covidwho-640079

ABSTRACT

BACKGROUND: The rate of ICU admission among patients with coronavirus varied from 3% to 100% and the mortality was as high as 86% of admitted patients. The objective of the systematic review was to investigate the rate of ICU admission, mortality, morbidity, and complications among patients with coronavirus. METHODS: A comprehensive strategy was conducted in PubMed/Medline; Science direct and LILACS from December 2002 to May 2020 without language restriction. The Heterogeneity among the included studies was checked with forest plot, χ2 test, I2 test, and the p-values. All observational studies reporting rate of ICU admission, the prevalence of mortality and its determinants among ICU admitted patients with coronavirus were included and the rest were excluded. RESULT: A total of 646 articles were identified from different databases and 50 articles were selected for evaluation. Thirty-seven Articles with 24983 participants were included. The rate of ICU admission was 32% (95% CI: 26 to 38, 37 studies and 32, 741 participants). The Meta-Analysis revealed that the pooled prevalence of mortality in patients with coronavirus disease in ICU was 39% (95% CI: 34 to 43, 37 studies and 24, 983 participants). CONCLUSION: The Meta-Analysis revealed that approximately one-third of patients admitted to ICU with severe Coronavirus disease and more than thirty percent of patients admitted to ICU with a severe form of COVID-19 for better care died which warns the health care stakeholders to give attention to intensive care patients. REGISTRATION: This Systematic review and Meta-Analysis was registered in Prospero international prospective register of systemic reviews (CRD42020177095) on April 9/2020.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Middle East Respiratory Syndrome Coronavirus/physiology , SARS Virus/physiology , Comorbidity , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Hospitalization , Humans , Intensive Care Units , Prevalence , Regression Analysis , Severity of Illness Index
8.
Eur Rev Med Pharmacol Sci ; 24(12): 7173-7191, 2020 06.
Article in English | MEDLINE | ID: covidwho-635637

ABSTRACT

OBJECTIVE: A new pandemic coronavirus causing coronavirus disease-2019 (COVID-19), initially called 2019-nCoV and successively named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The COVID-19 refers to the disease while the SARS-CoV-2 refers to the virus and is characterized by a rapid contagious capacity able to spread worldwide in a very short time. The rise in the number of infected patients and deaths is of great concern especially because symptoms are vague and similar to other forms of flu infection and corona syndrome infections characterized by fever, fatigue, dry cough, and dyspnea. According to the latest guidelines published by the World Health Organization (WHO), the diagnosis of COVID-19 must be confirmed by quantitative reverse transcription polymerase chain reaction (rRT-PCR) or gene sequencing of specimen obtained from throat, sputum and blood samples. However, the limitations due to logistics, as well as low sensitivity and specificity diagnostic tools currently available have been reported as the main cause of high incidence of either false-negative or positive results. PATIENTS AND METHODS: The purpose of the present translational research protocol is to discuss and present the original findings from our research team on new diagnostic technique to detect four Coronaviridae family members (SARS-CoV-2, SARS-CoV, HCoV and MERS-CoV), highlighting the methodology, the procedure and the possible advantages. Moreover, the authors review the current epidemiology, precautions and safety measures for health personnel to manage patients with known or suspected COVID-19 infection. RESULTS: Implementation of an effective and rapid plan of diagnosing, screening and checking is a key factor to reduce and prevent further transmission. This procedure based on rRT-PCR could be of great help to decisively validate the results obtained from more conventional diagnostic procedures such as chest computed tomography (CT) imaging and chest ultrasound. CONCLUSIONS: This translational diagnostic tool will assist emergency and primary care clinicians, as well as out-of-hospital providers, in effectively managing people with suspected or confirmed SARS-CoV-2.


Subject(s)
Coronavirus Infections/diagnosis , International Cooperation , Pneumonia, Viral/diagnosis , Translational Medical Research , Betacoronavirus/isolation & purification , Clinical Laboratory Techniques , Humans , Italy , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Pandemics , Reverse Transcriptase Polymerase Chain Reaction , SARS Virus/isolation & purification , Sensitivity and Specificity , Vietnam
9.
Am J Med Sci ; 360(1): 5-34, 2020 07.
Article in English | MEDLINE | ID: covidwho-634522

ABSTRACT

Since December 2019, the global pandemic caused by the highly infectious novel coronavirus 2019-nCoV (COVID-19) has been rapidly spreading. As of April 2020, the outbreak has spread to over 210 countries, with over 2,400,000 confirmed cases and over 170,000 deaths.1 COVID-19 causes a severe pneumonia characterized by fever, cough and shortness of breath. Similar coronavirus outbreaks have occurred in the past causing severe pneumonia like COVID-19, most recently, severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). However, over time, SARS-CoV and MERS-CoV were shown to cause extrapulmonary signs and symptoms including hepatitis, acute renal failure, encephalitis, myositis and gastroenteritis. Similarly, sporadic reports of COVID-19 related extrapulmonary manifestations emerge. Unfortunately, there is no comprehensive summary of the multiorgan manifestations of COVID-19, making it difficult for clinicians to quickly educate themselves about this highly contagious and deadly pathogen. What is more, is that SARS-CoV and MERS-CoV are the closest humanity has come to combating something similar to COVID-19, however, there exists no comparison between the manifestations of any of these novel coronaviruses. In this review, we summarize the current knowledge of the manifestations of the novel coronaviruses SARS-CoV, MERS-CoV and COVID-19, with a particular focus on the latter, and highlight their differences and similarities.


Subject(s)
Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Severe Acute Respiratory Syndrome/physiopathology , Betacoronavirus , Coronavirus Infections/epidemiology , Humans , Middle East Respiratory Syndrome Coronavirus , Pandemics , Pneumonia, Viral/epidemiology , SARS Virus , Severe Acute Respiratory Syndrome/epidemiology
11.
Brain Behav Immun ; 87: 18-22, 2020 07.
Article in English | MEDLINE | ID: covidwho-626360

ABSTRACT

Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.


Subject(s)
Coronavirus Infections/physiopathology , Nervous System Diseases/physiopathology , Pneumonia, Viral/physiopathology , Betacoronavirus , Consciousness Disorders/etiology , Consciousness Disorders/physiopathology , Coronavirus 229E, Human , Coronavirus Infections/complications , Coronavirus NL63, Human , Coronavirus OC43, Human , Dysgeusia/etiology , Dysgeusia/physiopathology , Encephalitis/etiology , Encephalitis/physiopathology , Encephalitis, Viral/etiology , Encephalitis, Viral/physiopathology , Guillain-Barre Syndrome/etiology , Guillain-Barre Syndrome/physiopathology , Humans , Middle East Respiratory Syndrome Coronavirus , Nervous System Diseases/etiology , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/physiopathology , Neurotoxicity Syndromes/virology , Olfaction Disorders/etiology , Olfaction Disorders/physiopathology , Pandemics , Pneumonia, Viral/complications , Polyneuropathies/etiology , Polyneuropathies/physiopathology , SARS Virus , Seizures/etiology , Seizures/physiopathology , Severe Acute Respiratory Syndrome/complications , Severe Acute Respiratory Syndrome/physiopathology , Stroke/etiology , Stroke/physiopathology
12.
Transfus Med Rev ; 34(2): 75-80, 2020 04.
Article in English | MEDLINE | ID: covidwho-622874

ABSTRACT

With the outbreak of unknown pneumonia in Wuhan, China, in December 2019, a new coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), aroused the attention of the entire world. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19). The World Health Organization declared COVID-19 in China as a Public Health Emergency of International Concern. Two other coronavirus infections-SARS in 2002-2003 and Middle East Respiratory Syndrome (MERS) in 2012-both caused severe respiratory syndrome in humans. All 3 of these emerging infectious diseases leading to a global spread are caused by ß-coronaviruses. Although coronaviruses usually infect the upper or lower respiratory tract, viral shedding in plasma or serum is common. Therefore, there is still a theoretical risk of transmission of coronaviruses through the transfusion of labile blood products. Because more and more asymptomatic infections are being found among COVID-19 cases, considerations of blood safety and coronaviruses have arisen especially in endemic areas. In this review, we detail current evidence and understanding of the transmission of SARS-CoV, MERS-CoV, and SARS-CoV-2 through blood products as of February 10, 2020, and also discuss pathogen inactivation methods on coronaviruses.


Subject(s)
Betacoronavirus , Blood Safety , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Asymptomatic Infections , China/epidemiology , Coronavirus Infections/blood , Humans , Middle East Respiratory Syndrome Coronavirus , Pneumonia, Viral/blood , Public Health , Risk , SARS Virus , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/prevention & control
13.
Microbes Infect ; 22(4-5): 226-229, 2020.
Article in English | MEDLINE | ID: covidwho-622092

ABSTRACT

During virus infection, host toll-like receptors (TLRs) can recognize different pathogen-associated molecular patterns and trigger the innate immune response. TLR7/8 can identify the single-stranded RNA (ssRNA) of the virus. This study aimed to search ssRNA sequences recognized by TLR7/8 from the SARS-CoV-2, SARS-CoV, and MERS-CoV whole genomes by a bioinformatic technique. The immunoinformatic approach showed that the SARS-CoV-2 genome has more ssRNA fragments that could be recognized by TLR7/8 than the SARS-CoV genome. These findings suggest innate immune hyperactivation by SARS-CoV-2. This activity is possibly able to provoke a robust proinflammatory response via TLR7/8 recognition and cause acute lung injury.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/virology , Middle East Respiratory Syndrome Coronavirus/physiology , Pneumonia, Viral/virology , SARS Virus/physiology , Toll-Like Receptor 7/physiology , Toll-Like Receptor 8/physiology , Computational Biology , Genome, Viral , Humans , Immunity, Innate , Pandemics , Virus Attachment
14.
PLoS One ; 15(5): e0232790, 2020.
Article in English | MEDLINE | ID: covidwho-616862

ABSTRACT

The Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) is an endemic virus in dromedaries. Annually, Saudi Arabia imports thousands of camels from the Horn of Africa, yet the epidemiology of MERS-CoV in these animals is largely unknown. Here, MERS-CoV prevalence was compared in imported African camels and their local counterparts. A total of 1399 paired sera and nasal swabs were collected from camels between 2016 and 2018. Imported animals from Sudan (n = 829) and Djibouti (n = 328) were sampled on incoming ships at Jeddah Islamic seaport before unloading, and local camels were sampled from Jeddah (n = 242). Samples were screened for neutralizing antibodies (nAbs) and MERS-CoV viral RNA. The overall seroprevalence was 92.7% and RNA detection rate was 17.2%. Imported camels had higher seroprevalence compared to resident herds (93.8% vs 87.6%, p <0.01) in contrast to RNA detection (13.3% vs 35.5%, p <0.0001). Seroprevalence significantly increased with age (p<0.0001) and viral RNA detection rate was ~2-folds higher in camels <2-year-old compared to older animals. RNA detection was higher in males verses females (24.3% vs 12.6%, p<0.0001) but seroprevalence was similar. Concurrent positivity for viral RNA and nAbs was found in >87% of the RNA positive animals, increased with age and was sex-dependent. Importantly, reduced viral RNA load was positively correlated with nAb titers. Our data confirm the widespread of MERS-CoV in imported and domestic camels in Saudi Arabia and highlight the need for continuous active surveillance and better prevention measures. Further studies are also warranted to understand camels correlates of protection for proper vaccine development.


Subject(s)
Antibodies, Viral/blood , Camelus/virology , Coronavirus Infections/epidemiology , Middle East Respiratory Syndrome Coronavirus/isolation & purification , RNA, Viral/blood , Animals , Antibodies, Neutralizing/blood , Coronavirus Infections/virology , Cross-Sectional Studies , Disease Reservoirs/virology , Djibouti/epidemiology , Female , Male , Middle East Respiratory Syndrome Coronavirus/genetics , Prevalence , Saudi Arabia/epidemiology , Seroepidemiologic Studies , Sudan/epidemiology
15.
Br J Radiol ; 93(1112): 20200515, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-614942

ABSTRACT

During the first two decades of the 21st century, there have been three coronavirus infection outbreaks raising global health concerns by severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the SARS-CoV-2. Although the reported imaging findings of coronavirus infection are variable and non-specific, the most common initial chest radiograph (CXR) and CT findings are ground-glass opacities and consolidation with peripheral predominance and eventually spread to involve both lungs as the disease progresses. These findings can be explained by the immune pathogenesis of coronavirus infection causing diffuse alveolar damage. Although it is insensitive in mild or early coronavirus infection, the CXR remains as the first-line and the most commonly used imaging modality. That is because it is rapid and easily accessible and helpful for monitoring patient progress during treatment. CT is more sensitive to detect early parenchymal lung abnormalities and disease progression, and can provide an alternative diagnosis. In this pictorial review, various coronavirus infection cases are presented to provide imaging spectrums of coronavirus infection and present differences in imaging among them or from other viral infections, and to discuss the role of imaging in viral infection outbreaks.


Subject(s)
Coronavirus Infections/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Severe Acute Respiratory Syndrome/diagnostic imaging , Adult , Aged , Betacoronavirus , Coronavirus Infections/epidemiology , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Middle East Respiratory Syndrome Coronavirus , Pandemics , Pneumonia, Viral/epidemiology , Radiography , SARS Virus , Severe Acute Respiratory Syndrome/epidemiology , Tomography, X-Ray Computed
16.
mSphere ; 5(3)2020 06 24.
Article in English | MEDLINE | ID: covidwho-612518

ABSTRACT

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has motivated an intensive analysis of its molecular epidemiology following its worldwide spread. To understand the early evolutionary events following its emergence, a data set of 985 complete SARS-CoV-2 sequences was assembled. Variants showed a mean of 5.5 to 9.5 nucleotide differences from each other, consistent with a midrange coronavirus substitution rate of 3 × 10-4 substitutions/site/year. Almost one-half of sequence changes were C→U transitions, with an 8-fold base frequency normalized directional asymmetry between C→U and U→C substitutions. Elevated ratios were observed in other recently emerged coronaviruses (SARS-CoV, Middle East respiratory syndrome [MERS]-CoV), and decreasing ratios were observed in other human coronaviruses (HCoV-NL63, -OC43, -229E, and -HKU1) proportionate to their increasing divergence. C→U transitions underpinned almost one-half of the amino acid differences between SARS-CoV-2 variants and occurred preferentially in both 5' U/A and 3' U/A flanking sequence contexts comparable to favored motifs of human APOBEC3 proteins. Marked base asymmetries observed in nonpandemic human coronaviruses (U ≫ A > G ≫ C) and low G+C contents may represent long-term effects of prolonged C→U hypermutation in their hosts. The evidence that much of sequence change in SARS-CoV-2 and other coronaviruses may be driven by a host APOBEC-like editing process has profound implications for understanding their short- and long-term evolution. Repeated cycles of mutation and reversion in favored mutational hot spots and the widespread occurrence of amino acid changes with no adaptive value for the virus represent a quite different paradigm of virus sequence change from neutral and Darwinian evolutionary frameworks and are not incorporated by standard models used in molecular epidemiology investigations.IMPORTANCE The wealth of accurately curated sequence data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its long genome, and its low substitution rate provides a relatively blank canvas with which to investigate effects of mutational and editing processes imposed by the host cell. The finding that a large proportion of sequence change in SARS-CoV-2 in the initial months of the pandemic comprised C→U mutations in a host APOBEC-like context provides evidence for a potent host-driven antiviral editing mechanism against coronaviruses more often associated with antiretroviral defense. In evolutionary terms, the contribution of biased, convergent, and context-dependent mutations to sequence change in SARS-CoV-2 is substantial, and these processes are not incorporated by standard models used in molecular epidemiology investigations.


Subject(s)
Betacoronavirus/genetics , Cytosine/analysis , Genome, Viral/genetics , Polymorphism, Single Nucleotide/genetics , Uracil/analysis , Base Composition/genetics , Base Sequence/genetics , Coronavirus Infections/pathology , Cytidine Deaminase/genetics , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Pandemics , Pneumonia, Viral/pathology , SARS Virus/genetics
17.
Med Sci (Paris) ; 36(6-7): 633-641, 2020.
Article in French | MEDLINE | ID: covidwho-611702

ABSTRACT

Coronavirus is a large family of viruses that infect mammals and birds. Coronaviruses are known to cross barrier species and infect new ones. In the past twenty years, we witnessed the emergence of three different coronaviruses, the latest one being the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for the COVID-19 (covid disease 19) pandemic. Coronaviruses are enveloped virus with a long positive sense RNA genome. Like all viruses, they hijack the cellular machinery to replicate and produce new virions. There is no approved vaccine or specific antiviral molecule against coronaviruses but with the urgency to treat COVID-19, several candidate therapies are currently investigated.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Virus Physiological Phenomena , Animals , Betacoronavirus/classification , Betacoronavirus/physiology , Betacoronavirus/ultrastructure , Coronavirus Infections/drug therapy , Epidemics , Humans , Middle East Respiratory Syndrome Coronavirus , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS Virus , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/virology , Viral Structural Proteins/chemistry , Zoonoses/epidemiology , Zoonoses/virology
18.
Med Sci (Paris) ; 36(6-7): 633-641, 2020.
Article in French | MEDLINE | ID: covidwho-607023

ABSTRACT

Coronavirus is a large family of viruses that infect mammals and birds. Coronaviruses are known to cross barrier species and infect new ones. In the past twenty years, we witnessed the emergence of three different coronaviruses, the latest one being the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for the COVID-19 (covid disease 19) pandemic. Coronaviruses are enveloped virus with a long positive sense RNA genome. Like all viruses, they hijack the cellular machinery to replicate and produce new virions. There is no approved vaccine or specific antiviral molecule against coronaviruses but with the urgency to treat COVID-19, several candidate therapies are currently investigated.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Virus Physiological Phenomena , Animals , Betacoronavirus/classification , Betacoronavirus/physiology , Betacoronavirus/ultrastructure , Coronavirus Infections/drug therapy , Epidemics , Humans , Middle East Respiratory Syndrome Coronavirus , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS Virus , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/virology , Viral Structural Proteins/chemistry , Zoonoses/epidemiology , Zoonoses/virology
19.
J Korean Med Sci ; 35(23): e220, 2020 Jun 15.
Article in English | MEDLINE | ID: covidwho-598890

ABSTRACT

BACKGROUND: The absence of effective antiviral medications and vaccines increased the focus on non-pharmaceutical preventive behaviors for mitigating against the coronavirus disease 2019 (COVID-19) pandemic. To examine the current status of non-pharmaceutical preventive behaviors practiced during the COVID-19 outbreak and factors affecting behavioral activities, we compared to the 2015 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in Korea. METHODS: This was a serial cross-sectional population-based study in Korea with four surveys conducted on June 2 and 25, 2015 (MERS-CoV surveys), and February 4, and April 2, 2020 (COVID-19 surveys). Of 25,711 participants selected using random digit dialing numbers, 4,011 participants (aged ≥ 18 years) were successfully interviewed, for the 2020 COVID-19 (n = 2,002) and 2015 MERS-CoV (n = 2,009) epidemics were included. Participants were selected post-stratification by sex, age, and province. The total number of weighted cases in this survey equaled the total number of unweighted cases at the national level. We measured the levels of preventive behaviors (social distancing [avoiding physical contact with others]), and practicing transmission-reducing behaviors such as wearing face mask and handwashing. RESULTS: Between the surveys, respondents who reported practicing social distancing increased from 41.9%-58.2% (MERS-CoV) to 83.4%-92.3% (COVID-19). The response rate for the four surveys ranged between 13.7% and 17.7%. Practicing transmission-reducing behaviors (wearing face masks and handwashing) at least once during COVID-19 (78.8%, 80.2%) also increased compared to that during MERS-CoV (15.5%, 60.3%). The higher affective risk perception groups were more likely to practice transmission-reducing measures (adjusted odds ratio, 3.24-4.81; 95 confidence interval, 1.76-6.96) during both COVID-19 and MERS-CoV. CONCLUSION: The study findings suggest markedly increased proportions of non-pharmaceutical behavioral practices evenly across all subgroups during the two different novel virus outbreaks in Korea. Strategic interventions are needed to attempt based on preventive behavior works.


Subject(s)
Communicable Disease Control , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Hand Disinfection/methods , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Protective Clothing/statistics & numerical data , Adult , Betacoronavirus , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Middle East Respiratory Syndrome Coronavirus , Pandemics/prevention & control , Primary Prevention/methods , Republic of Korea/epidemiology , Surveys and Questionnaires , Young Adult
20.
Viruses ; 12(6)2020 06 15.
Article in English | MEDLINE | ID: covidwho-598456

ABSTRACT

As more cases of COVID-19 are studied and treated worldwide, it had become apparent that the lethal and most severe cases of pneumonia are due to an out-of-control inflammatory response to the SARS-CoV-2 virus. I explored the putative causes of this specific feature through a detailed genomic comparison with the closest SARS-CoV-2 relatives isolated from bats, as well as previous coronavirus strains responsible for the previous epidemics (SARS-CoV and MERS-CoV). The high variability region of the nsp3 protein was confirmed to exhibit the most variations between closest strains. It was then studied in the context of physiological and molecular data available in the literature. A number of convergent findings suggest de-mono-ADP-ribosylation (de-MARylation) of STAT1 by the SARS-CoV-2 nsp3 as a putative cause of the cytokine storm observed in the most severe cases of COVID-19. This may suggest new therapeutic approaches and help in designing assays to predict the virulence of naturally circulating SARS-like animal coronaviruses.


Subject(s)
ADP-Ribosylation/physiology , Betacoronavirus/genetics , Cytokine Release Syndrome/pathology , STAT1 Transcription Factor/metabolism , Viral Nonstructural Proteins/metabolism , Amino Acid Sequence/genetics , Coronavirus Infections/pathology , Humans , Inflammation/pathology , Inflammation/virology , Middle East Respiratory Syndrome Coronavirus/genetics , Pandemics , Peptidyl-Dipeptidase A/biosynthesis , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/pathology , SARS Virus/genetics , Sequence Homology , Viral Nonstructural Proteins/genetics
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