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1.
Nat Commun ; 12(1): 780, 2021 02 16.
Article in English | MEDLINE | ID: covidwho-1087442

ABSTRACT

Novel pathogenic coronaviruses - such as SARS-CoV and probably SARS-CoV-2 - arise by homologous recombination between co-infecting viruses in a single cell. Identifying possible sources of novel coronaviruses therefore requires identifying hosts of multiple coronaviruses; however, most coronavirus-host interactions remain unknown. Here, by deploying a meta-ensemble of similarity learners from three complementary perspectives (viral, mammalian and network), we predict which mammals are hosts of multiple coronaviruses. We predict that there are 11.5-fold more coronavirus-host associations, over 30-fold more potential SARS-CoV-2 recombination hosts, and over 40-fold more host species with four or more different subgenera of coronaviruses than have been observed to date at >0.5 mean probability cut-off (2.4-, 4.25- and 9-fold, respectively, at >0.9821). Our results demonstrate the large underappreciation of the potential scale of novel coronavirus generation in wild and domesticated animals. We identify high-risk species for coronavirus surveillance.


Subject(s)
Coronavirus/physiology , Host-Pathogen Interactions , Mammals/virology , Animals , Coronavirus Infections/virology , Humans , Models, Biological , Phylogeny , Recombination, Genetic/genetics , Reproducibility of Results
2.
Onderstepoort J Vet Res ; 88(1): e1-e8, 2021 Feb 10.
Article in English | MEDLINE | ID: covidwho-1077469

ABSTRACT

Human coronaviruses are known respiratory pathogens associated with a range of respiratory illnesses, and there are considerable morbidity and hospitalisation amongst immune-compromised individuals of all age groups. The emergence of a highly pathogenic human coronavirus in China in 2019 has confirmed the long-held opinion that these viruses are important emerging and re-emerging pathogens. In this review article, we trace the discovery and emergence of coronaviruses (CoVs) over time since they were first reported. The review article will enrich our understanding on the host range, diversity and evolution, transmission of human CoVs and the threat posed by these viruses circulating in animal populations but overtime have spilled over to humans because of the increased proximity between humans and animals.


Subject(s)
Communicable Diseases, Emerging/virology , Coronavirus Infections/virology , Coronavirus/classification , Animals , Coronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Disease Outbreaks , Host Specificity , Humans
3.
Cell ; 184(1): 120-132.e14, 2021 01 07.
Article in English | MEDLINE | ID: covidwho-1064914

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has claimed the lives of over one million people worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a member of the Coronaviridae family of viruses that can cause respiratory infections of varying severity. The cellular host factors and pathways co-opted during SARS-CoV-2 and related coronavirus life cycles remain ill defined. To address this gap, we performed genome-scale CRISPR knockout screens during infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E). These screens uncovered host factors and pathways with pan-coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, sterol regulatory element-binding protein (SREBP) signaling, bone morphogenetic protein (BMP) signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VMP1, TMEM41, and TMEM64 (VTT) domain-containing protein transmembrane protein 41B (TMEM41B) for infection by SARS-CoV-2 and three seasonal coronaviruses. This human coronavirus host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus pandemics.


Subject(s)
Coronavirus Infections/genetics , Genome-Wide Association Study , /physiology , A549 Cells , Cell Line , Clustered Regularly Interspaced Short Palindromic Repeats , Coronavirus 229E, Human/physiology , Coronavirus Infections/virology , Coronavirus NL63, Human/physiology , Coronavirus OC43, Human/physiology , Gene Knockout Techniques , HEK293 Cells , Host-Pathogen Interactions/drug effects , Humans , Membrane Proteins/metabolism , Metabolic Networks and Pathways/drug effects , Protein Interaction Mapping
4.
Cell ; 184(1): 106-119.e14, 2021 01 07.
Article in English | MEDLINE | ID: covidwho-1064913

ABSTRACT

The Coronaviridae are a family of viruses that cause disease in humans ranging from mild respiratory infection to potentially lethal acute respiratory distress syndrome. Finding host factors common to multiple coronaviruses could facilitate the development of therapies to combat current and future coronavirus pandemics. Here, we conducted genome-wide CRISPR screens in cells infected by SARS-CoV-2 as well as two seasonally circulating common cold coronaviruses, OC43 and 229E. This approach correctly identified the distinct viral entry factors ACE2 (for SARS-CoV-2), aminopeptidase N (for 229E), and glycosaminoglycans (for OC43). Additionally, we identified phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis as critical host pathways supporting infection by all three coronaviruses. By contrast, the lysosomal protein TMEM106B appeared unique to SARS-CoV-2 infection. Pharmacological inhibition of phosphatidylinositol kinases and cholesterol homeostasis reduced replication of all three coronaviruses. These findings offer important insights for the understanding of the coronavirus life cycle and the development of host-directed therapies.


Subject(s)
/genetics , Coronavirus Infections/genetics , Coronavirus/physiology , Genome-Wide Association Study , Host-Pathogen Interactions , /physiology , A549 Cells , Animals , Biosynthetic Pathways/drug effects , Cell Line , Chlorocebus aethiops , Cholesterol/biosynthesis , Cholesterol/metabolism , Cluster Analysis , Clustered Regularly Interspaced Short Palindromic Repeats , Common Cold/genetics , Common Cold/virology , Coronavirus/classification , Coronavirus Infections/virology , Gene Knockout Techniques , Host-Pathogen Interactions/drug effects , Humans , Mice , Phosphatidylinositols/biosynthesis , Vero Cells , Virus Internalization/drug effects , Virus Replication
5.
Nat Commun ; 12(1): 141, 2021 01 08.
Article in English | MEDLINE | ID: covidwho-1065862

ABSTRACT

Coronaviruses spike (S) glycoproteins mediate viral entry into host cells by binding to host receptors. However, how the S1 subunit undergoes conformational changes for receptor recognition has not been elucidated in Alphacoronavirus. Here, we report the cryo-EM structures of the HCoV-229E S trimer in prefusion state with two conformations. The activated conformation may pose the potential exposure of the S1-RBDs by decreasing of the interaction area between the S1-RBDs and the surrounding S1-NTDs and S1-RBDs compared to the closed conformation. Furthermore, structural comparison of our structures with the previously reported HCoV-229E S structure showed that the S trimers trended to open the S2 subunit from the closed conformation to open conformation, which could promote the transition from pre- to postfusion. Our results provide insights into the mechanisms involved in S glycoprotein-mediated Alphacoronavirus entry and have implications for vaccine and therapeutic antibody design.


Subject(s)
CD13 Antigens/metabolism , Coronavirus 229E, Human/physiology , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization , Cell Line, Tumor , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Cryoelectron Microscopy , Humans , Models, Molecular , Protein Conformation, alpha-Helical , Protein Multimerization/physiology , Protein Structure, Quaternary , Protein Subunits/metabolism , Spike Glycoprotein, Coronavirus/ultrastructure
6.
J Infect Public Health ; 14(1): 123-130, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1065353

ABSTRACT

BACKGROUND: The aim of this research is to assess the predictive accuracy of the Infectious Diseases Seeker (IDS) - an innovative tool for prompt identification of the causative agent of infectious diseases during outbreaks - when field epidemiological data collected from a novel outbreak of unknown origin are analysed by the tool. For this reason, it has been taken into account the novel coronavirus disease (COVID-19) outbreak, which began in China at the end of December 2019, has rapidly spread around the globe, and it has led to a public health emergency of international concern (PHEIC), declared to the 30th of January 2020 by the World Health Organization (WHO). METHODS: The IDS takes advantage of an off-line database, built before the COVID-19 pandemic, which represents a pivotal characteristic for working without an internet connection. The software has been tested using the epidemiological data available in different and progressive stages of the COVID-19 outbreak. As a comparison, the results of the tests performed using the epidemiological data from the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) epidemic in 2002 and Middle East Respiratory Syndrome coronavirus (MERS-CoV) epidemic in 2012, are shown. RESULTS: The overall outcomes provided by the software are comforting, as a matter of the fact that IDS has identified with a good accuracy the SARS and MERS epidemics (over 90%), while, as expected, it has not provided erroneous and equivocal readings after the elaboration COVID-19 epidemic data. CONCLUSIONS: Even though IDS has not recognized the COVID-19 epidemic, it has not given to the end user a false result and wrong interpretation, as expected by the developers. For this reason, IDS reveals itself as useful software to identify a possible epidemic or outbreak. Thus, the intention of developers is to plan, once the software will be released, dedicated updates and upgrades of the database (e.g., SARS-CoV-2) in order to keep this tool increasingly useful and applicable to reality.


Subject(s)
/epidemiology , Databases, Factual , Population Surveillance , /virology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Disease Outbreaks , Global Health , Humans , Middle East Respiratory Syndrome Coronavirus , SARS Virus
7.
PLoS One ; 16(2): e0246150, 2021.
Article in English | MEDLINE | ID: covidwho-1061213

ABSTRACT

A coronavirus pandemic caused by a novel coronavirus (SARS-CoV-2) has spread rapidly worldwide since December 2019. Improved understanding and new strategies to cope with novel coronaviruses are urgently needed. Viruses (especially RNA viruses) encode a limited number and size (length of polypeptide chain) of viral proteins and must interact with the host cell components to control (hijack) the host cell machinery. To achieve this goal, the extensive mimicry of SLiMs in host proteins provides an effective strategy. However, little is known regarding SLiMs in coronavirus proteins and their potential targets in host cells. The objective of this study is to uncover SLiMs in coronavirus proteins that are present within host cells. These SLiMs have a high possibility of interacting with host intracellular proteins and hijacking the host cell machinery for virus replication and dissemination. In total, 1,479 SLiM hits were identified in the 16 proteins of 590 coronaviruses infecting humans. Overall, 106 host proteins were identified that may interact with SLiMs in 16 coronavirus proteins. These SLiM-interacting proteins are composed of many intracellular key regulators, such as receptors, transcription factors and kinases, and may have important contributions to virus replication, immune evasion and viral pathogenesis. A total of 209 pathways containing proteins that may interact with SLiMs in coronavirus proteins were identified. This study uncovers potential mechanisms by which coronaviruses hijack the host cell machinery. These results provide potential therapeutic targets for viral infections.


Subject(s)
Coronavirus Infections/pathology , Middle East Respiratory Syndrome Coronavirus/metabolism , SARS Virus/metabolism , Viral Proteins/metabolism , Amino Acid Motifs , Coronavirus Infections/virology , Databases, Protein , Humans , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Phylogeny , Protein Interaction Domains and Motifs , Proteins/chemistry , Proteins/classification , SARS Virus/isolation & purification , Signal Transduction/genetics , User-Computer Interface , Viral Proteins/chemistry , Viral Proteins/classification
8.
Acta Chim Slov ; 67(3): 949-956, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1060696

ABSTRACT

Due to the current spreading of the new disease CoViD-19, the World Health Organization formally declared a world pandemic on March 11, 2020. The present trends indicate that the pandemic will have an enormous clinical and economic impact on population health. Infections are initiated by the transmembrane spike (S) glycoproteins of human coronavirus (hCoV) binding to host receptors. Ongoing research and therapeutic product development are of vital importance for the successful treatment of CoViD-19. To contribute somewhat to the overall effort, herein, single point mutations (SPMs) of the binding site residues in hCoV-OC43 S that recognizes cellular surface components containing 9-O-acetylated sialic acid (9-O-Ac-Sia) are explored using an in silico protein engineering approach, while their effects on the binding of 9-O-Ac-Sia and Hidroxychloroquine (Hcq) are evaluated using molecular docking simulations. Thr31Met and Val84Arg are predicted to be the critical - most likely SPMs in hCoV-OC43 S for the binding of 9-O-Ac-Sia and Hcq, respectively, even though Thr31Met is a very likely SPM in the case of Hcq too. The corresponding modes of interaction indicate a comparable strength of the Thr31Met/9-O-Ac-Sia and Val84Arg/Hcq (or Thr31Met/Hcq) complexes. Given that the binding site is conserved in all CoV S glycoproteins that associate with 9-O-acetyl-sialoglycans, the high hydrophobic affinity of Hcq to hCoV-OC43 S speaks in favor of its ability to competitively inhibit rapid S-mediated virion attachment in high-density receptor environments, but its considerably low specificity to hCoV-OC43 S may be one of the key obstacles in considering the potential of Hcq to become a drug candidate.


Subject(s)
Coronavirus Infections/virology , Coronavirus OC43, Human/genetics , Hydroxychloroquine/metabolism , Point Mutation , Sialic Acids/metabolism , Spike Glycoprotein, Coronavirus/genetics , Binding Sites , Coronavirus Infections/metabolism , Coronavirus OC43, Human/chemistry , Coronavirus OC43, Human/metabolism , Humans , Molecular Docking Simulation/methods , Protein Engineering , /genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
9.
Cells ; 10(2)2021 02 02.
Article in English | MEDLINE | ID: covidwho-1060037

ABSTRACT

Many viruses disrupt host gene expression by degrading host mRNAs and/or manipulating translation activities to create a cellular environment favorable for viral replication. Often, virus-induced suppression of host gene expression, including those involved in antiviral responses, contributes to viral pathogenicity. Accordingly, clarifying the mechanisms of virus-induced disruption of host gene expression is important for understanding virus-host cell interactions and virus pathogenesis. Three highly pathogenic human coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and SARS-CoV-2, have emerged in the past two decades. All of them encode nonstructural protein 1 (nsp1) in their genomes. Nsp1 of SARS-CoV and MERS-CoV exhibit common biological functions for inducing endonucleolytic cleavage of host mRNAs and inhibition of host translation, while viral mRNAs evade the nsp1-induced mRNA cleavage. SARS-CoV nsp1 is a major pathogenic determinant for this virus, supporting the notion that a viral protein that suppresses host gene expression can be a virulence factor, and further suggesting the possibility that SARS-CoV-2 nsp1, which has high amino acid identity with SARS-CoV nsp1, may serve as a major virulence factor. This review summarizes the gene expression suppression functions of nsp1 of CoVs, with a primary focus on SARS-CoV nsp1 and MERS-CoV nsp1.


Subject(s)
Betacoronavirus , Coronavirus Infections/virology , Viral Nonstructural Proteins/physiology , Animals , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , Gene Expression Regulation , Host Microbial Interactions , Humans , Mice , RNA, Messenger/genetics , Virus Replication
10.
Allergol Immunopathol (Madr) ; 49(1): 159-164, 2021.
Article in English | MEDLINE | ID: covidwho-1059768

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a disease caused by a new strain of coronavirus named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Globally, since the outbreak, more than seven million confirmed cases of COVID-19 have been reported. The rapid spread and increase in the number of new cases is due to person-to-person transmission. To further control its transmission, early laboratory diagnosis of both asymptomatic and symptomatic patients is crucial. Presently, the COVID-19 diagnosis of infected individuals is dependent on computed tomography scanning and real-time polymerase chain reaction (PCR). The latter is considered more sensitive and efficient for early diagnosis. In this review, general comparisons are made (cases, fatality rate, incubation period, clinical features, and reservoirs) and diagnostic laboratory procedures (specimens, extraction methods, and positive rates by real-time PCR) are compared between SARS, Middle East Respiratory Syndrome, and SARS-2. In total, 8982 SARS-2 suspected patients specimen data were retrieved, in which 40.9% (n = 3678) were detected as positive by real-time PCR. The specimen-wise high detection rate was observed from bronchoalveolar lavage, followed by saliva, nasal swabs, and sputum. As the COVID-19 cases are persistently increasing, the selection of appropriate specimens and laboratory assay would help in rapid and timely diagnosis.


Subject(s)
/diagnosis , Real-Time Polymerase Chain Reaction , /isolation & purification , Bronchoalveolar Lavage , /virology , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Humans , Nasopharynx/virology , Saliva/virology , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/virology , Sputum/virology
11.
BMC Bioinformatics ; 22(1): 18, 2021 Jan 07.
Article in English | MEDLINE | ID: covidwho-1059737

ABSTRACT

BACKGROUND: The ongoing global COVID-19 pandemic is caused by SARS-CoV-2, a novel coronavirus first discovered at the end of 2019. It has led to more than 50 million confirmed cases and more than 1 million deaths across 219 countries as of 11 November 2020, according to WHO statistics. SARS-CoV-2, SARS-CoV, and MERS-CoV are similar. They are highly pathogenic and threaten public health, impair the economy, and inflict long-term impacts on society. No drug or vaccine has been approved as a treatment for these viruses. Efforts to develop antiviral measures have been hampered by the insufficient understanding of how the human body responds to viral infections at the cellular and molecular levels. RESULTS: In this study, journal articles and transcriptomic and proteomic data surveying coronavirus infections were collected. Response genes and proteins were then identified by differential analyses comparing gene/protein levels between infected and control samples. Finally, the H2V database was created to contain the human genes and proteins that respond to SARS-CoV-2, SARS-CoV, and MERS-CoV infection. CONCLUSIONS: H2V provides molecular information about the human response to infection. It can be a powerful tool to discover cellular pathways and processes relevant for viral pathogenesis to identify potential drug targets. It is expected to accelerate the process of antiviral agent development and to inform preparations for potential future coronavirus-related emergencies. The database is available at: http://www.zhounan.org/h2v .


Subject(s)
/metabolism , Coronavirus Infections/metabolism , Databases, Genetic , Databases, Protein , Severe Acute Respiratory Syndrome/metabolism , User-Computer Interface , /genetics , /virology , Coronavirus Infections/genetics , Coronavirus Infections/pathology , Coronavirus Infections/virology , Humans , Middle East Respiratory Syndrome Coronavirus/physiology , Proteomics , SARS Virus/physiology , Severe Acute Respiratory Syndrome/genetics , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/virology
12.
PLoS One ; 16(1): e0246084, 2021.
Article in English | MEDLINE | ID: covidwho-1050493

ABSTRACT

The Nicaraguan COVID-19 situation is exceptional for Central America. The government restricts testing and testing supplies, and the true extent of the coronavirus crisis remains unknown. Dozens of deaths have been reported among health-care workers. However, statistics on the crisis' effect on health-care workers and their risk of being infected with SARS-CoV-2 are lacking. We aimed to estimate the prevalence of SARS-CoV-2 infection in health-care workers and to examine correlations with risk factors such as age, sex and comorbidities. Study participants (N = 402, median age 38.48 years) included physicians, nurses and medical assistants, from public and private hospitals, independent of symptom presentation. SARS-CoV-2 was detected on saliva samples using the loop-mediated isothermal amplification assay. A questionnaire was employed to determine subjects' COVID-19-associated symptoms and their vulnerability to complications from risk factors such as age, sex, professional role and comorbidities. The study was performed five weeks into the exponential growth period in Nicaragua. We discovered that 30.35% of health-care workers participating in our study had been infected with SARS-CoV-2. A large percentage (54.92%) of those who tested positive were asymptomatic and were still treating patients. Nearly 50% of health-care workers who tested positive were under 40, an astonishing 30.33% reported having at least one comorbidity. In our study, sex and age are important risk factors for the probability of testing positive for SARS-CoV-2 with significance being greatest among those between 30 and 40 years of age. In general, being male resulted in higher risk. Our data are the first non-governmental data obtained in Nicaragua. They shed light on several important aspects of COVID-19 in an underdeveloped nation whose government has implemented a herd-immunity strategy, while lacking an adequate healthcare system and sufficient PPE for health-care workers. These data are important for creating policies for containing the spread of SARS-CoV-2.


Subject(s)
/epidemiology , Health Personnel/statistics & numerical data , Adult , Aged , Asymptomatic Diseases/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Humans , Infectious Disease Transmission, Patient-to-Professional/statistics & numerical data , Male , Middle Aged , Nicaragua/epidemiology , Prevalence , Risk Factors , Saliva/virology
13.
Arch Virol ; 166(3): 929-933, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1046769

ABSTRACT

This is the first study of respiratory infections in Córdoba, Argentina, caused by endemic human coronavirus (HCoV)-OC43 and HCOV-229E, which circulated during 2011-2012 at a 3% rate, either as single or multiple infections. They were detected mainly in children, but HCoV-229E was also found in adults. HCoV-229E was detected in five out of 631 samples (0.8%), and HCoV-OC43 was found in 14 out of 631 (2.2%) samples. Clinical manifestations ranged from fever to respiratory distress, and a significant association of HCoV-229E with asthma was observed. Further studies and surveillance are needed to provide better clinical insights, early diagnosis, and medical care of patients, as well as to contribute to epidemiology modeling and prevention.


Subject(s)
Common Cold/epidemiology , Coronavirus 229E, Human/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus OC43, Human/isolation & purification , Adolescent , Adult , Aged , Argentina , Child , Child, Preschool , Common Cold/virology , Coronavirus 229E, Human/genetics , Coronavirus Infections/virology , Coronavirus OC43, Human/genetics , Cross-Sectional Studies , Humans , Infant , Middle Aged , Retrospective Studies , Seasons , Young Adult
14.
Cell Rep ; 34(7): 108737, 2021 02 16.
Article in English | MEDLINE | ID: covidwho-1046536

ABSTRACT

In the ongoing coronavirus disease 2019 (COVID-19) pandemic, there remain unanswered questions regarding the nature and significance of the humoral immune response toward other coronavirus infections. Here, we investigate the cross-reactivity of antibodies raised against the first severe acute respiratory syndrome coronavirus (SARS-CoV) for their reactivity toward SARS-CoV-2. We extensively characterize a selection of 10 antibodies covering all of the SARS-CoV structural proteins: spike, membrane, nucleocapsid, and envelope. Although nearly all of the examined SARS-CoV antibodies display some level of reactivity to SARS-CoV-2, we find only partial cross-neutralization for the spike antibodies. The implications of our work are two-fold. First, we establish a set of antibodies with known reactivity to both SARS-CoV and SARS-CoV-2, which will allow further study of both viruses. Second, we provide empirical evidence of the high propensity for antibody cross-reactivity between distinct strains of human coronaviruses, which is critical information for designing diagnostic and vaccine strategies for COVID-19.


Subject(s)
Antibodies, Viral/immunology , SARS Virus/immunology , Spike Glycoprotein, Coronavirus/immunology , /immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cross Reactions/immunology , HEK293 Cells , Humans , Immunity, Humoral/immunology , Pandemics , SARS Virus/genetics , Spike Glycoprotein, Coronavirus/genetics
15.
BMC Biol ; 19(1): 12, 2021 01 22.
Article in English | MEDLINE | ID: covidwho-1044598

ABSTRACT

BACKGROUND: Pandemics, even more than other medical problems, require swift integration of knowledge. When caused by a new virus, understanding the underlying biology may help finding solutions. In a setting where there are a large number of loosely related projects and initiatives, we need common ground, also known as a "commons." Wikidata, a public knowledge graph aligned with Wikipedia, is such a commons and uses unique identifiers to link knowledge in other knowledge bases. However, Wikidata may not always have the right schema for the urgent questions. In this paper, we address this problem by showing how a data schema required for the integration can be modeled with entity schemas represented by Shape Expressions. RESULTS: As a telling example, we describe the process of aligning resources on the genomes and proteomes of the SARS-CoV-2 virus and related viruses as well as how Shape Expressions can be defined for Wikidata to model the knowledge, helping others studying the SARS-CoV-2 pandemic. How this model can be used to make data between various resources interoperable is demonstrated by integrating data from NCBI (National Center for Biotechnology Information) Taxonomy, NCBI Genes, UniProt, and WikiPathways. Based on that model, a set of automated applications or bots were written for regular updates of these sources in Wikidata and added to a platform for automatically running these updates. CONCLUSIONS: Although this workflow is developed and applied in the context of the COVID-19 pandemic, to demonstrate its broader applicability it was also applied to other human coronaviruses (MERS, SARS, human coronavirus NL63, human coronavirus 229E, human coronavirus HKU1, human coronavirus OC4).


Subject(s)
/pathology , Genomics/methods , Knowledge Bases , Proteomics/methods , /physiology , /metabolism , Coronavirus/genetics , Coronavirus/physiology , Coronavirus Infections/metabolism , Coronavirus Infections/pathology , Coronavirus Infections/virology , Genome, Viral , Humans , Internet , Pandemics , Viral Proteins/genetics , Viral Proteins/metabolism , Workflow
16.
Infect Genet Evol ; 88: 104708, 2021 03.
Article in English | MEDLINE | ID: covidwho-1039486

ABSTRACT

The pandemic due to novel coronavirus, SARS-CoV-2 is a serious global concern now. More than thousand new COVID-19 infections are getting reported daily for this virus across the globe. Thus, the medical research communities are trying to find the remedy to restrict the spreading of this virus, while the vaccine development work is still under research in parallel. In such critical situation, not only the medical research community, but also the scientists in different fields like microbiology, pharmacy, bioinformatics and data science are also sharing effort to accelerate the process of vaccine development, virus prediction, forecasting the transmissible probability and reproduction cases of virus for social awareness. With the similar context, in this article, we have studied sequence variability of the virus primarily focusing on three aspects: (a) sequence variability among SARS-CoV-1, MERS-CoV and SARS-CoV-2 in human host, which are in the same coronavirus family, (b) sequence variability of SARS-CoV-2 in human host for 54 different countries and (c) sequence variability between coronavirus family and country specific SARS-CoV-2 sequences in human host. For this purpose, as a case study, we have performed topological analysis of 2391 global genomic sequences of SARS-CoV-2 in association with SARS-CoV-1 and MERS-CoV using an integrated semi-alignment based computational technique. The results of the semi-alignment based technique are experimentally and statistically found similar to alignment based technique and computationally faster. Moreover, the outcome of this analysis can help to identify the nations with homogeneous SARS-CoV-2 sequences, so that same vaccine can be applied to their heterogeneous human population.


Subject(s)
/epidemiology , Coronavirus Infections/epidemiology , Genetic Variation , Genome, Viral , Pandemics , Severe Acute Respiratory Syndrome/epidemiology , Africa/epidemiology , Americas/epidemiology , Asia/epidemiology , Australia/epidemiology , Base Sequence , /virology , Computational Biology/methods , Coronavirus Infections/transmission , Coronavirus Infections/virology , Europe/epidemiology , Host-Pathogen Interactions/genetics , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/pathogenicity , SARS Virus/genetics , SARS Virus/pathogenicity , Sequence Alignment , Severe Acute Respiratory Syndrome/transmission , Severe Acute Respiratory Syndrome/virology
17.
PLoS Pathog ; 17(1): e1009226, 2021 01.
Article in English | MEDLINE | ID: covidwho-1034956

ABSTRACT

Recombination is proposed to be critical for coronavirus (CoV) diversity and emergence of SARS-CoV-2 and other zoonotic CoVs. While RNA recombination is required during normal CoV replication, the mechanisms and determinants of CoV recombination are not known. CoVs encode an RNA proofreading exoribonuclease (nsp14-ExoN) that is distinct from the CoV polymerase and is responsible for high-fidelity RNA synthesis, resistance to nucleoside analogues, immune evasion, and virulence. Here, we demonstrate that CoVs, including SARS-CoV-2, MERS-CoV, and the model CoV murine hepatitis virus (MHV), generate extensive and diverse recombination products during replication in culture. We show that the MHV nsp14-ExoN is required for native recombination, and that inactivation of ExoN results in decreased recombination frequency and altered recombination products. These results add yet another critical function to nsp14-ExoN, highlight the uniqueness of the evolved coronavirus replicase, and further emphasize nsp14-ExoN as a central, completely conserved, and vulnerable target for inhibitors and attenuation of SARS-CoV-2 and future emerging zoonotic CoVs.


Subject(s)
/drug therapy , Coronavirus Infections/drug therapy , Exoribonucleases/pharmacology , Virus Replication/drug effects , Antiviral Agents/pharmacology , Coronavirus Infections/virology , Exoribonucleases/genetics , Humans , Recombination, Genetic/drug effects , Viral Nonstructural Proteins/genetics , Virus Replication/genetics
18.
Jpn J Infect Dis ; 73(5): 377-380, 2020 Sep 24.
Article in English | MEDLINE | ID: covidwho-1034439

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a severe infectious disease of the respiratory tract caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2, and has a high mortality rate. The disease emerged from Wuhan, China, in late 2019, and spread to Japan, including Hokkaido, in January 2020. In February 2020, 3 children were diagnosed with COVID-19 in Furano, Hokkaido, Japan. During this period, influenza and human metapneumovirus infections were prevalent among children in the Furano region. Two of the 3 patients experienced co-infection with other respiratory viruses, including influenza virus A or human metapneumovirus. To the authors' knowledge, the cases described in the present report were the first pediatric patients with COVID-19 in Japan. In children with COVID-19, the possibility of co-infection with other respiratory pathogens should be considered.


Subject(s)
Coinfection/diagnosis , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Respiratory Tract Infections/diagnosis , Betacoronavirus/isolation & purification , Child , Child, Preschool , Coinfection/pathology , Coinfection/virology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Humans , Japan/epidemiology , Lung/diagnostic imaging , Lung/pathology , Male , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Respiratory Tract Infections/pathology , Respiratory Tract Infections/virology
19.
Public Health ; 190: 132-134, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1033173

ABSTRACT

OBJECTIVES: The impact of the COVID-19 pandemic in Scotland has been amongst the most severe in Europe. Serological surveillance is critical to determine the overall extent of infection across populations and to inform the public health response. This study aimed to estimate the proportion of people who have antibodies to SARS-CoV-2 ('seroprevalence') in the general population of Scotland and to see if this changes over time. STUDY DESIGN/METHODS: Between International Organization for Standardization (ISO) week 17 (i.e. week commencing 20th April) and ISO week 25 (week commencing 15 June), 4751 residual blood samples were obtained from regional biochemistry laboratories in six participating regional health authority areas covering approximately 75% of the Scottish population. Samples were tested for the presence of anti-SARS-CoV-2 IgG antibodies using the LIAISON®SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Italy). Seroprevalence rates were adjusted for the sensitivity and specificity of the assay using Bayesian methods. RESULTS: The combined adjusted seroprevalence across the study period was 4.3% (95% confidence interval: 4.2%-4.5%). The proportion varied each week between 1.9% and 6.8% with no difference in antibody positivity by age, sex or geographical area. CONCLUSIONS: At the end of the first wave of the COVID-19 pandemic, only a small fraction of the Scottish population had antibodies to SARS-CoV-2. Control of COVID-19 requires the ability to detect asymptomatic and mild infections that would otherwise remain undetected through existing surveillance systems. This is important to determine the true number of infections within the general population which, in turn, can help to understand transmission, inform control measures and provide a denominator for the estimation of severity measures such as the proportion of infected people who have been hospitalised and/or have died.


Subject(s)
Antibodies, Viral/blood , Coronavirus Infections/virology , Immunoglobulin G/blood , Pandemics , Population Surveillance/methods , /immunology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Prevalence , Public Health Surveillance , Scotland/epidemiology , Seroepidemiologic Studies , Serologic Tests/methods
20.
J Med Internet Res ; 23(1): e24097, 2021 01 15.
Article in English | MEDLINE | ID: covidwho-1032503

ABSTRACT

BACKGROUND: Digital communication technologies are playing an important role in the health communication strategies of governments and public health authorities during the COVID-19 pandemic. The internet and social media have become important sources of health-related information on COVID-19 and on protective behaviors. In addition, the COVID-19 infodemic is spreading faster than the coronavirus itself, which interferes with governmental health-related communication efforts. This jeopardizes national public health containment strategies. Therefore, digital health literacy is a key competence to navigate web-based COVID-19-related information and service environments. OBJECTIVE: This study aimed to investigate university students' digital health literacy and web-based information-seeking behaviors during the early stages of the COVID-19 pandemic in Germany. METHODS: A cross-sectional study among 14,916 university students aged ≥18 years from 130 universities across all 16 federal states of Germany was conducted using a web-based survey. Along with sociodemographic characteristics (sex, age, subjective social status), the measures included five subscales from the Digital Health Literacy Instrument (DHLI), which was adapted to the specific context of the COVID-19 pandemic. Web-based information-seeking behavior was investigated by examining the web-based sources used by university students and the topics that the students searched for in connection with COVID-19. Data were analyzed using univariate and bivariate analyses. RESULTS: Across digital health literacy dimensions, the greatest difficulties could be found for assessing the reliability of health-related information (5964/14,103, 42.3%) and the ability to determine whether the information was written with a commercial interest (5489/14,097, 38.9%). Moreover, the respondents indicated that they most frequently have problems finding the information they are looking for (4282/14,098, 30.4%). When stratified according to sociodemographic characteristics, significant differences were found, with female university students reporting a lower DHLI for the dimensions of "information searching" and "evaluating reliability." Search engines, news portals, and websites of public bodies were most often used by the respondents as sources to search for information on COVID-19 and related issues. Female students were found to use social media and health portals more frequently, while male students used Wikipedia and other web-based encyclopedias as well as YouTube more often. The use of social media was associated with a low ability to critically evaluate information, while the opposite was observed for the use of public websites. CONCLUSIONS: Although digital health literacy is well developed in university students, a significant proportion of students still face difficulties with certain abilities to evaluate information. There is a need to strengthen the digital health literacy capacities of university students using tailored interventions. Improving the quality of health-related information on the internet is also key.


Subject(s)
/epidemiology , Health Literacy/methods , Information Seeking Behavior/physiology , Internet/standards , Adult , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Cross-Sectional Studies , Female , Germany , Humans , Male , Reproducibility of Results , Students , Surveys and Questionnaires , Young Adult
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