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The Yale Journal of Biology and Medicine Dec 1974
Review
Topics: Adolescent; Adult; Age Factors; Animals; Antibodies, Viral; Cell Line; Child, Preschool; Common Cold; Complement Fixation Tests; Coronaviridae; Hemagglutination Inhibition Tests; Humans; Infant; Infant, Newborn; Male; Neutralization Tests; Time Factors; United States; Virus Diseases
PubMed: 4617423
DOI: No ID Found -
Advances in Virus Research 1983Coronaviruses have recently emerged as an important group of animal and human pathogens that share a distinctive replicative cycle. Some of the unique characteristics in... (Comparative Study)
Comparative Study Review
Coronaviruses have recently emerged as an important group of animal and human pathogens that share a distinctive replicative cycle. Some of the unique characteristics in the replication of coronaviruses include generation of a 3' coterminal-nested set of five or six subgenomic mRNAs, each of which appears to direct the synthesis of one protein. Two virus-specific RNA polymerase activities have been identified. Many of the distinctive features of coronavirus infection and coronavirus-induced diseases may result from the properties of the two coronavirus glycoproteins. The intracellular budding site, which may be important in the establishment and maintenance of persistent infections, appears to be due to the restricted intracytoplasmic migration of the E1 glycoprotein, which acts as a matrix-like transmembrane glycoprotein. E1 also exhibits distinctive behavior by self-aggregating on heating at 100°C in sodium dodecyl sulfate (SDS) and by its interaction with RNA in the viral nucleocapsid. The E1 of mouse hepatitis virus (MHV) is an -linked glycoprotein, unlike most other viral glycoproteins. Thus, the coronavirus system may be a useful model for the study of synthesis, glycosylation, and transport of -linked cellular glycoproteins.
Topics: Coronaviridae; Glycoproteins; Lipid Metabolism; RNA, Viral; Viral Proteins; Virus Replication
PubMed: 6362367
DOI: 10.1016/s0065-3527(08)60721-6 -
Experientia Dec 1987Although a very wide range of viral diseases exists in vertebrates, certain generalizations can be made regarding pathogenetic pathways on the molecular level. The... (Review)
Review
Although a very wide range of viral diseases exists in vertebrates, certain generalizations can be made regarding pathogenetic pathways on the molecular level. The presentation will focus on interactions of virions and their components with target cells. Using coronaviruses as examples the changes in virulence have been traced back to single mutational events; recombination, however, is likely to be an alternative mechanism by which virus-host interactions (e.g. the cell-, organ- or animal species-spectrum) can dramatically change. Receptor molecules are essential for the early interactions during infection and some of these have been identified. Events in the target cell and the host organism are discussed, and wherever possible, aspects of virus evolution and cooperation between infectious agents are highlighted.
Topics: Adsorption; Animals; Coronaviridae; Coronaviridae Infections; Cytopathogenic Effect, Viral; Endocytosis; Genes, Viral; Humans; Receptors, Virus; Virus Diseases
PubMed: 2826215
DOI: 10.1007/BF01945522 -
Antiviral Research Jan 2014In 2002/2003, a novel coronavirus (CoV) caused a pandemic, infecting more than 8000 people, of whom nearly 10% died. This virus, termed severe acute respiratory... (Review)
Review
In 2002/2003, a novel coronavirus (CoV) caused a pandemic, infecting more than 8000 people, of whom nearly 10% died. This virus, termed severe acute respiratory syndrome-CoV was linked to a zoonotic origin from rhinolophid bats in 2005. Since then, numerous studies have described novel bat CoVs, including close relatives of the newly emerging Middle East respiratory syndrome (MERS)-CoV. In this paper we discuss CoV genomic properties and compare different taxonomic approaches in light of the technical difficulties of obtaining full genomic sequences directly from bat specimens. We first present an overview of the available studies on bat CoVs, with details on their chiropteran hosts, then comparatively analyze the increase in bat CoV studies and novel genomic sequences obtained since the SARS pandemic. We then conduct a comprehensive phylogenetic analysis of the genera Alpha- and Betacoronavirus, to show that bats harbour more CoV diversity than other mammalian hosts and are widely represented in most, but not all parts of the tree of mammalian CoVs. We next discuss preliminary evidence for phylogenetic co-segregation of CoVs and bat hosts encompassing the Betacoronavirus clades b and d, with an emphasis on the sampling bias that exists among bat species and other mammals, then present examples of CoVs infecting different hosts on the one hand and viruses apparently confined to host genera on the other. We also demonstrate a geographic bias within available studies on bat CoVs, and identify a critical lack of information from biodiversity hotspots in Africa, Asia and Latin America. We then present evidence for a zoonotic origin of four of the six known human CoVs (HCoV), three of which likely involved bats, namely SARS-CoV, MERS-CoV and HCoV-229E; compare the available data on CoV pathogenesis in bats to that in other mammalian hosts; and discuss hypotheses on the putative insect origins of CoV ancestors. Finally, we suggest caution with conclusions on the zoonotic potential of bat viruses, based only on genomic sequence data, and emphasize the need to preserve these ecologically highly relevant animals. This paper forms part of a symposium in Antiviral Research on "from SARS to MERS: 10years of research on highly pathogenic human coronaviruses".
Topics: Africa; Animals; Asia; Chiroptera; Cluster Analysis; Coronaviridae; Coronavirus Infections; Ecology; Evolution, Molecular; Genome, Viral; Humans; Latin America; Middle East; Phylogeography; Zoonoses
PubMed: 24184128
DOI: 10.1016/j.antiviral.2013.10.013 -
Drug Discovery Today Apr 2020Human coronaviruses (CoVs) are enveloped viruses with a positive-sense single-stranded RNA genome. Currently, six human CoVs have been reported including human... (Review)
Review
Human coronaviruses (CoVs) are enveloped viruses with a positive-sense single-stranded RNA genome. Currently, six human CoVs have been reported including human coronavirus 229E (HCoV-229E), OC43 (HCoV-OC43), NL63 (HCoV-NL63), HKU1 (HCoV-HKU1), severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and MiddleEast respiratory syndrome (MERS) coronavirus (MERS-CoV). They cause moderate to severe respiratory and intestinal infections in humans. In this review, we focus on recent advances in the research and development of small-molecule anti-human coronavirus therapies targeting different stages of the CoV life cycle.
Topics: Animals; Antiviral Agents; Coronaviridae Infections; Coronavirus; Drug Design; Drug Development; Humans; Molecular Structure; Molecular Targeted Therapy; Structure-Activity Relationship
PubMed: 32006468
DOI: 10.1016/j.drudis.2020.01.015 -
Intervirology 1978
Topics: Animals; Coronaviridae; Coronaviridae Infections; Ecology; Humans; Lipids; Molecular Weight; Peptides; RNA, Viral; Viral Proteins; Virus Replication
PubMed: 213397
DOI: 10.1159/000148996 -
Virus Research Apr 2015Coronaviruses are a large group of enveloped, single-stranded positive-sense RNA viruses that infect a wide range of avian and mammalian species, including humans. The... (Review)
Review
Coronaviruses are a large group of enveloped, single-stranded positive-sense RNA viruses that infect a wide range of avian and mammalian species, including humans. The emergence of deadly human coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) have bolstered research in these viral and often zoonotic pathogens. While coronavirus cell and tissue tropism, host range, and pathogenesis are initially controlled by interactions between the spike envelope glycoprotein and host cell receptor, it is becoming increasingly apparent that proteolytic activation of spike by host cell proteases also plays a critical role. Coronavirus spike proteins are the main determinant of entry as they possess both receptor binding and fusion functions. Whereas binding to the host cell receptor is an essential first step in establishing infection, the proteolytic activation step is often critical for the fusion function of spike, as it allows for controlled release of the fusion peptide into target cellular membranes. Coronaviruses have evolved multiple strategies for proteolytic activation of spike, and a large number of host proteases have been shown to proteolytically process the spike protein. These include, but are not limited to, endosomal cathepsins, cell surface transmembrane protease/serine (TMPRSS) proteases, furin, and trypsin. This review focuses on the diversity of strategies coronaviruses have evolved to proteolytically activate their fusion protein during spike protein biosynthesis and the critical entry step of their life cycle, and highlights important findings on how proteolytic activation of coronavirus spike influences tissue and cell tropism, host range and pathogenicity.
Topics: Coronaviridae; Host Specificity; Host-Pathogen Interactions; Humans; Peptide Hydrolases; Proteolysis; Spike Glycoprotein, Coronavirus; Viral Tropism
PubMed: 25445340
DOI: 10.1016/j.virusres.2014.11.021 -
Current Opinion in Genetics &... Dec 1991The explosive pace of sequencing of RNA viruses is leading to rapid advances in our understanding of the evolution of these viruses and of the ways in which their... (Comparative Study)
Comparative Study Review
The explosive pace of sequencing of RNA viruses is leading to rapid advances in our understanding of the evolution of these viruses and of the ways in which their genomes are organized and expressed. New insights are coming not only from genomic nucleotide sequence comparisons, but also from direct sequencing of transcribed mRNAs and of RNAs that serve as intermediates in replication.
Topics: Biological Evolution; Coronaviridae; Genes, Viral; Genome, Viral; Paramyxoviridae; Plant Viruses; RNA Viruses; RNA, Viral; Viral Structural Proteins; Virus Replication
PubMed: 1822281
DOI: 10.1016/s0959-437x(05)80196-0 -
Journal of Virology Jun 2023Coronavirus genome replication and expression are mediated by the viral replication-transcription complex (RTC) which is assembled from multiple nonstructural proteins...
Coronavirus genome replication and expression are mediated by the viral replication-transcription complex (RTC) which is assembled from multiple nonstructural proteins (nsp). Among these, nsp12 represents the central functional subunit. It harbors the RNA-directed RNA polymerase (RdRp) domain and contains, at its N terminus, an additional domain called NiRAN which is widely conserved in coronaviruses and other nidoviruses. In this study, we produced bacterially expressed coronavirus nsp12s to investigate and compare NiRAN-mediated NMPylation activities from representative alpha- and betacoronaviruses. We found that the four coronavirus NiRAN domains characterized to date have a number of conserved properties, including (i) robust nsp9-specific NMPylation activities that appear to operate largely independently of the C-terminal RdRp domain, (ii) nucleotide substrate preference for UTP followed by ATP and other nucleotides, (iii) dependence on divalent metal ions, with Mn being preferred over Mg, and (iv) a key role of N-terminal residues (particularly Asn2) of nsp9 for efficient formation of a covalent phosphoramidate bond between NMP and the N-terminal amino group of nsp9. In this context, a mutational analysis confirmed the conservation and critical role of Asn2 across different subfamilies of the family , as shown by studies using chimeric coronavirus nsp9 variants in which six N-terminal residues were replaced with those from other corona-, pito- and letovirus nsp9 homologs. The combined data of this and previous studies reveal a remarkable degree of conservation among coronavirus NiRAN-mediated NMPylation activities, supporting a key role of this enzymatic activity in viral RNA synthesis and processing. There is strong evidence that coronaviruses and other large nidoviruses evolved a number of unique enzymatic activities, including an additional RdRp-associated NiRAN domain, that are conserved in nidoviruses but not in most other RNA viruses. Previous studies of the NiRAN domain mainly focused on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and suggested different functions for this domain, such as NMPylation/RNAylation of nsp9, RNA guanylyltransferase activities involved in canonical and/or unconventional RNA capping pathways, and other functions. To help resolve partly conflicting information on substrate specificities and metal ion requirements reported previously for the SARS-CoV-2 NiRAN NMPylation activity, we extended these earlier studies by characterizing representative alpha- and betacoronavirus NiRAN domains. The study revealed that key features of NiRAN-mediated NMPylation activities, such as protein and nucleotide specificity and metal ion requirements, are very well conserved among genetically divergent coronaviruses, suggesting potential avenues for future antiviral drug development targeting this essential viral enzyme.
Topics: Humans; Nucleotides; RNA, Viral; RNA-Dependent RNA Polymerase; SARS-CoV-2; Viral Nonstructural Proteins; Coronaviridae; Protein Domains; Viral Proteins; Conserved Sequence; Protein Structure, Secondary; Vero Cells
PubMed: 37199624
DOI: 10.1128/jvi.00465-23 -
Viruses Feb 2023SARS-CoV-2, a novel betacoronavirus strain, has caused a pandemic that has claimed the lives of nearly 6.7M people worldwide. Vaccines and medicines are being developed...
SARS-CoV-2, a novel betacoronavirus strain, has caused a pandemic that has claimed the lives of nearly 6.7M people worldwide. Vaccines and medicines are being developed around the world to reduce the disease spread, fatality rates, and control the new variants. Understanding the protein-protein interaction mechanism of SARS-CoV-2 in humans, and their comparison with the previous SARS-CoV and MERS strains, is crucial for these efforts. These interactions might be used to assess vaccination effectiveness, diagnose exposure, and produce effective biotherapeutics. Here, we present the HuCoPIA database, which contains approximately 100,000 protein-protein interactions between humans and three strains (SARS-CoV-2, SARS-CoV, and MERS) of betacoronavirus. The interactions in the database are divided into common interactions between all three strains and those unique to each strain. It also contains relevant functional annotation information of human proteins. The HuCoPIA database contains SARS-CoV-2 (41,173), SARS-CoV (31,997), and MERS (26,862) interactions, with functional annotation of human proteins like subcellular localization, tissue-expression, KEGG pathways, and Gene ontology information. We believe HuCoPIA will serve as an invaluable resource to diverse experimental biologists, and will help to advance the research in better understanding the mechanism of betacoronaviruses.
Topics: Humans; Coronaviridae; SARS-CoV-2; COVID-19; Ascomycota; Databases, Factual
PubMed: 36851706
DOI: 10.3390/v15020492