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1.
Nat Commun ; 11(1): 4235, 2020 08 25.
Article in English | MEDLINE | ID: covidwho-738373

ABSTRACT

Bats are presumed reservoirs of diverse coronaviruses (CoVs) including progenitors of Severe Acute Respiratory Syndrome (SARS)-CoV and SARS-CoV-2, the causative agent of COVID-19. However, the evolution and diversification of these coronaviruses remains poorly understood. Here we use a Bayesian statistical framework and a large sequence data set from bat-CoVs (including 630 novel CoV sequences) in China to study their macroevolution, cross-species transmission and dispersal. We find that host-switching occurs more frequently and across more distantly related host taxa in alpha- than beta-CoVs, and is more highly constrained by phylogenetic distance for beta-CoVs. We show that inter-family and -genus switching is most common in Rhinolophidae and the genus Rhinolophus. Our analyses identify the host taxa and geographic regions that define hotspots of CoV evolutionary diversity in China that could help target bat-CoV discovery for proactive zoonotic disease surveillance. Finally, we present a phylogenetic analysis suggesting a likely origin for SARS-CoV-2 in Rhinolophus spp. bats.


Subject(s)
Chiroptera/virology , Coronavirus Infections/veterinary , Coronavirus/genetics , Evolution, Molecular , Zoonoses/transmission , Animals , Bayes Theorem , Betacoronavirus/classification , Betacoronavirus/genetics , Biodiversity , China , Chiroptera/classification , Coronavirus/classification , Coronavirus Infections/transmission , Coronavirus Infections/virology , Humans , Pandemics , Phylogeny , Phylogeography , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Zoonoses/virology
2.
Med Sci (Paris) ; 36(8-9): 783-796, 2020.
Article in French | MEDLINE | ID: covidwho-706965

ABSTRACT

SARS-CoV-2 is a new human coronavirus (CoV), which emerged in People's Republic of China at the end of 2019 and is responsible for the global Covid-19 pandemic that caused more than 540 000 deaths in six months. Understanding the origin of this virus is an important issue and it is necessary to determine the mechanisms of its dissemination in order to be able to contain new epidemics. Based on phylogenetic inferences, sequence analysis and structure-function relationships of coronavirus proteins, informed by the knowledge currently available, we discuss the different scenarios evoked to account for the origin - natural or synthetic - of the virus. On the basis of currently available data, it is impossible to determine whether SARS-CoV-2 is the result of a natural zoonotic emergence or an accidental escape from experimental strains. Regardless of its origin, the study of the evolution of the molecular mechanisms involved in the emergence of this pandemic virus is essential to develop therapeutic and vaccine strategies.


Subject(s)
Betacoronavirus/genetics , Communicable Diseases, Emerging/virology , Coronavirus Infections/virology , Coronavirus/classification , Evolution, Molecular , Pandemics , Phylogeny , Pneumonia, Viral/virology , RNA, Viral/genetics , Amino Acid Sequence , Animals , Betacoronavirus/classification , Betacoronavirus/isolation & purification , Biohazard Release , China/epidemiology , Coronaviridae Infections/transmission , Coronaviridae Infections/veterinary , Coronaviridae Infections/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Disease Reservoirs , Gain of Function Mutation , Genome, Viral , HIV/genetics , Host Specificity , Humans , Mammals/virology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Reassortant Viruses/genetics , Sequence Alignment , Sequence Homology, Amino Acid , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/physiology , Zoonoses
3.
Viruses ; 12(8)2020 08 05.
Article in English | MEDLINE | ID: covidwho-696041

ABSTRACT

Zoonoses can constitute a threat for public health that can have a global importance, as seen with the current COVID-19 pandemic of severe acute respiratory syndrome coronavirus (SARS-CoV2). Bats have been recognized as an important reservoir of zoonotic coronaviruses (CoVs). In West Africa, where there is a high diversity of bat species, little is known on the circulation of CoVs in these hosts, especially at the interface with human populations. In this study, in Guinea, we tested a total of 319 bats belonging to 14 genera and six families of insectivorous and frugivorous bats across the country, for the presence of coronaviruses. We found CoVs in 35 (11%) of the tested bats-in three insectivorous bat species and five fruit bat species that were mostly captured close to human habitat. Positivity rates varied from 5.7% to 100%, depending on bat species. A wide diversity of alpha and beta coronaviruses was found across the country, including three sequences belonging to SarbeCoVs and MerbeCoVs subgenera known to harbor highly pathogenic human coronaviruses. Our findings suggest that CoVs are widely spread in West Africa and their circulation should be assessed to evaluate the risk of exposure of potential zoonotic CoVs to humans.


Subject(s)
Chiroptera/virology , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Coronavirus/classification , Coronavirus/genetics , Animals , Betacoronavirus/isolation & purification , Biodiversity , Coronavirus/isolation & purification , Female , Genome, Viral , Guinea , Humans , Male , Pandemics , Phylogeny , Pilot Projects , Pneumonia, Viral/veterinary , Pneumonia, Viral/virology , Zoonoses/virology
4.
Nat Commun ; 11(1): 3618, 2020 07 17.
Article in English | MEDLINE | ID: covidwho-651635

ABSTRACT

Global emergencies caused by the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle-East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2 significantly endanger human health. The spike (S) glycoprotein is the key antigen and its conserved S2 subunit contributes to viral entry by mediating host-viral membrane fusion. However, structural information of the post-fusion S2 from these highly pathogenic human-infecting coronaviruses is still lacking. We used single-particle cryo-electron microscopy to show that the post-fusion SARS-CoV S2 forms a further rotated HR1-HR2 six-helix bundle and a tightly bound linker region upstream of the HR2 motif. The structures of pre- and post-fusion SARS-CoV S glycoprotein dramatically differ, resembling that of the Mouse hepatitis virus (MHV) and other class I viral fusion proteins. This structure suggests potential targets for the development of vaccines and therapies against a wide range of SARS-like coronaviruses.


Subject(s)
Betacoronavirus/chemistry , Betacoronavirus/physiology , Spike Glycoprotein, Coronavirus/chemistry , Amino Acid Motifs , Coronavirus/chemistry , Coronavirus/classification , Coronavirus Infections/virology , Cryoelectron Microscopy , Humans , Membrane Fusion , Models, Molecular , Pandemics , Pneumonia, Viral/virology , Protein Conformation , Protein Multimerization , Virus Internalization
5.
Euro Surveill ; 25(26)2020 07.
Article in English | MEDLINE | ID: covidwho-639489

ABSTRACT

Following SARS-CoV-2 emergence in China, a specific surveillance was implemented in France. Phylogenetic analysis of sequences retrieved through this surveillance suggests that detected initial introductions, involving non-clade G viruses, did not seed local transmission. Nevertheless, identification of clade G variants subsequently circulating in the country, with the earliest from a patient who neither travelled to risk areas nor had contact with travellers, suggests that SARS-CoV-2 might have been present before the first recorded local cases.


Subject(s)
Coronavirus Infections/genetics , Coronavirus/genetics , Disease Outbreaks/prevention & control , Sentinel Surveillance , Betacoronavirus , Coronavirus/classification , Coronavirus/isolation & purification , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , France/epidemiology , Genome, Viral/genetics , Humans , Pandemics/prevention & control , Phylogeny , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis , Viral Proteins/genetics
6.
Phys Med ; 75: 83-84, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-607295

ABSTRACT

In the current pandemic times, medical physicists may not be aware that there is an interesting story on two significant discoveries related to the coronavirus. One is the invention of the polymerase chain reaction (PCR) and the other is the first electron microscopic observation and identification of the coronavirus. Both of them were disregarded by the reviewers and major journals declined to publish these discoveries. These days, PCR, for example, is a widespread method for analyzing DNA, having a profound effect on healthcare, especially now during the Covid-19 pandemic. Prejudice or perhaps ignorance prevail in every aspect of our society, and there is no exception in scientific research. We need to, however, learn from these two stories and be open-minded about novel discoveries and findings - as they may be just disruptive in the "right" way to lead to an unexpected breakthrough.


Subject(s)
Coronavirus , Periodicals as Topic/history , Prejudice/history , Scholarly Communication/history , Coronavirus/classification , Coronavirus/ultrastructure , Coronavirus Infections , History, 20th Century , Humans , Microscopy, Immunoelectron/history , Pandemics , Pneumonia, Viral , Polymerase Chain Reaction/history
7.
Genes (Basel) ; 11(6)2020 06 09.
Article in English | MEDLINE | ID: covidwho-591861

ABSTRACT

The severe respiratory disease COVID-19 was initially reported in Wuhan, China, in December 2019, and spread into many provinces from Wuhan. The corresponding pathogen was soon identified as a novel coronavirus named SARS-CoV-2 (formerly, 2019-nCoV). As of 2 May, 2020, over 3 million COVID-19 cases had been confirmed, and 235,290 deaths had been reported globally, and the numbers are still increasing. It is important to understand the phylogenetic relationship between SARS-CoV-2 and known coronaviruses, and to identify its hosts for preventing the next round of emergency outbreak. In this study, we employ an effective alignment-free approach, the Natural Vector method, to analyze the phylogeny and classify the coronaviruses based on genomic and protein data. Our results show that SARS-CoV-2 is closely related to, but distinct from the SARS-CoV branch. By analyzing the genetic distances from the SARS-CoV-2 strain to the coronaviruses residing in animal hosts, we establish that the most possible transmission path originates from bats to pangolins to humans.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/transmission , Coronavirus/genetics , Models, Biological , Pneumonia, Viral/transmission , Animals , Betacoronavirus/classification , Chiroptera/virology , Coronavirus/classification , Coronavirus Infections/virology , Cysteine Endopeptidases/chemistry , Cysteine Endopeptidases/genetics , Disease Outbreaks , Disease Reservoirs , Humans , Mammals/classification , Mammals/virology , Pandemics , Phylogeny , Pneumonia, Viral/virology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/genetics
8.
PLoS Biol ; 18(6): e3000715, 2020 06.
Article in English | MEDLINE | ID: covidwho-574821

ABSTRACT

Zoonotic coronavirus (CoV) infections, such as those responsible for the current severe acute respiratory syndrome-CoV 2 (SARS-CoV-2) pandemic, cause grave international public health concern. In infected cells, the CoV RNA-synthesizing machinery associates with modified endoplasmic reticulum membranes that are transformed into the viral replication organelle (RO). Although double-membrane vesicles (DMVs) appear to be a pan-CoV RO element, studies to date describe an assortment of additional CoV-induced membrane structures. Despite much speculation, it remains unclear which RO element(s) accommodate viral RNA synthesis. Here we provide detailed 2D and 3D analyses of CoV ROs and show that diverse CoVs essentially induce the same membrane modifications, including the small open double-membrane spherules (DMSs) previously thought to be restricted to gamma- and delta-CoV infections and proposed as sites of replication. Metabolic labeling of newly synthesized viral RNA followed by quantitative electron microscopy (EM) autoradiography revealed abundant viral RNA synthesis associated with DMVs in cells infected with the beta-CoVs Middle East respiratory syndrome-CoV (MERS-CoV) and SARS-CoV and the gamma-CoV infectious bronchitis virus. RNA synthesis could not be linked to DMSs or any other cellular or virus-induced structure. Our results provide a unifying model of the CoV RO and clearly establish DMVs as the central hub for viral RNA synthesis and a potential drug target in CoV infection.


Subject(s)
Coronavirus Infections/pathology , Coronavirus Infections/virology , Coronavirus/classification , Coronavirus/physiology , Endoplasmic Reticulum/pathology , Endoplasmic Reticulum/virology , Virus Replication , Animals , Betacoronavirus/genetics , Betacoronavirus/physiology , Cell Line , Chlorocebus aethiops , Electron Microscope Tomography , Endoplasmic Reticulum/ultrastructure , Humans , Middle East Respiratory Syndrome Coronavirus/physiology , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , RNA, Viral/metabolism , Vero Cells
10.
Avian Pathol ; 49(4): 313-316, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-526536

ABSTRACT

Coronaviruses (CoVs) mainly cause enteric and/or respiratory signs. Mammalian CoVs including COVID-19 (now officially named SARS-CoV-2) belong to either the Alphacoronavirus or Betacoronavirus genera. In birds, the majority of the known CoVs belong to the Gammacoronavirus genus, whilst a small number are classified as Deltacoronaviruses. Gammacoronaviruses continue to be reported in an increasing number of avian species, generally by detection of viral RNA. Apart from infectious bronchitis virus in chickens, the only avian species in which CoV has been definitively associated with disease are the turkey, pheasant and guinea fowl. Whilst there is strong evidence for recombination between gammacoronaviruses of different avian species, and between betacoronaviruses in different mammals, evidence of recombination between coronaviruses of different genera is lacking. Furthermore, the recombination of an alpha or betacoronavirus with a gammacoronavirus is extremely unlikely. For recombination to happen, the two viruses would need to be present in the same cell of the same animal at the same time, a highly unlikely scenario as they cannot replicate in the same host!


Subject(s)
Bird Diseases/virology , Coronavirus Infections/veterinary , Coronavirus/classification , Gammacoronavirus/classification , Animals , Birds , Chickens , Coronavirus Infections/virology , Galliformes , Humans , Turkeys
11.
J Clin Virol ; 129: 104470, 2020 08.
Article in English | MEDLINE | ID: covidwho-478301

ABSTRACT

In Italy, the first SARS-CoV-2 infections were diagnosed in Rome, Lazio region, at the end of January 2020, but sustained transmission occurred later, since the end of February. From 1 February to 12 April 2020, 17,164 nasopharyngeal swabs were tested by real time PCR for the presence of SARS-CoV-2 at the Laboratory of Virology of National Institute for Infectious Diseases "Lazzaro Spallanzani" (INMI) in Rome. In the same period, coincident with the winter peak of influenza and other respiratory illnesses, 847 samples were analyzed by multiplex PCR assay for the presence of common respiratory pathogens. In our study the time trend of SARS-CoV-2 and that of other respiratory pathogens in the same observation period were analysed. Overall, results obtained suggest that the spread of the pandemic SARS-CoV-2 virus did not substantially affect the time trend of other respiratory infections in our region, highlighting no significant difference in rates of SARS-CoV-2 infection in patients with or without other respiratory pathogens. Therefore, in the present scenario of COVID-19 pandemic, differential diagnosis resulting positive for common respiratory pathogen(s) should not exclude testing of SARS-CoV-2.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus/isolation & purification , Influenza, Human/epidemiology , Nasopharynx/virology , Orthomyxoviridae/isolation & purification , Respiratory Tract Infections/epidemiology , Coronavirus/classification , Coronavirus Infections/virology , Humans , Influenza, Human/virology , Multiplex Polymerase Chain Reaction , Orthomyxoviridae/classification , Respiratory Tract Infections/virology , Rome/epidemiology
12.
F1000Res ; 9: 285, 2020.
Article in English | MEDLINE | ID: covidwho-619112

ABSTRACT

SARS-CoV-2 is the coronavirus agent of the COVID-19 pandemic causing high mortalities. In contrast, the widely spread human coronaviruses OC43, HKU1, 229E, and NL63 tend to cause only mild symptoms. The present study shows, by in silico analysis, that these common human viruses are expected to induce immune memory against SARS-CoV-2 by sharing protein fragments (antigen epitopes) for presentation to the immune system by MHC class I. A list of such epitopes is provided. The number of these epitopes and the prevalence of the common coronaviruses suggest that a large part of the world population has some degree of specific immunity against SARS-CoV-2 already, even without having been infected by that virus. For inducing protection, booster vaccinations enhancing existing immunity are less demanding than primary vaccinations against new antigens. Therefore, for the discussion on vaccination strategies against COVID-19, the available immune memory against related viruses should be part of the consideration.


Subject(s)
Antigens, Viral/immunology , Coronavirus Infections/immunology , Immunologic Memory , Pneumonia, Viral/immunology , Betacoronavirus , Coronavirus/classification , Epitopes/immunology , Humans , Pandemics
13.
mBio ; 11(3)2020 05 29.
Article in English | MEDLINE | ID: covidwho-432175

ABSTRACT

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was recently identified as the causative agent for the coronavirus disease 2019 (COVID-19) outbreak that has generated a global health crisis. We use a combination of genomic analysis and sensitive profile-based sequence and structure analysis to understand the potential pathogenesis determinants of this virus. As a result, we identify several fast-evolving genomic regions that might be at the interface of virus-host interactions, corresponding to the receptor binding domain of the Spike protein, the three tandem Macro fold domains in ORF1a, and the uncharacterized protein ORF8. Further, we show that ORF8 and several other proteins from alpha- and beta-CoVs belong to novel families of immunoglobulin (Ig) proteins. Among them, ORF8 is distinguished by being rapidly evolving, possessing a unique insert, and having a hypervariable position among SARS-CoV-2 genomes in its predicted ligand-binding groove. We also uncover numerous Ig domain proteins from several unrelated metazoan viruses, which are distinct in sequence and structure but share comparable architectures to those of the CoV Ig domain proteins. Hence, we propose that SARS-CoV-2 ORF8 and other previously unidentified CoV Ig domain proteins fall under the umbrella of a widespread strategy of deployment of Ig domain proteins in animal viruses as pathogenicity factors that modulate host immunity. The rapid evolution of the ORF8 Ig domain proteins points to a potential evolutionary arms race between viruses and hosts, likely arising from immune pressure, and suggests a role in transmission between distinct host species.IMPORTANCE The ongoing COVID-19 pandemic strongly emphasizes the need for a more complete understanding of the biology and pathogenesis of its causative agent SARS-CoV-2. Despite intense scrutiny, several proteins encoded by the genomes of SARS-CoV-2 and other SARS-like coronaviruses remain enigmatic. Moreover, the high infectivity and severity of SARS-CoV-2 in certain individuals make wet-lab studies currently challenging. In this study, we used a series of computational strategies to identify several fast-evolving regions of SARS-CoV-2 proteins which are potentially under host immune pressure. Most notably, the hitherto-uncharacterized protein encoded by ORF8 is one of them. Using sensitive sequence and structural analysis methods, we show that ORF8 and several other proteins from alpha- and beta-coronavirus comprise novel families of immunoglobulin domain proteins, which might function as potential immune modulators to delay or attenuate the host immune response against the viruses.


Subject(s)
Coronavirus/genetics , Coronavirus/pathogenicity , Evolution, Molecular , Viral Proteins/genetics , Virulence Factors/genetics , Amino Acid Sequence , Animals , Betacoronavirus/chemistry , Betacoronavirus/classification , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , Coronavirus/chemistry , Coronavirus/classification , Genome, Viral/genetics , Host Specificity , Humans , Immunoglobulin Domains/genetics , Models, Molecular , Open Reading Frames , Phylogeny , Viral Proteins/chemistry , Virulence Factors/chemistry
14.
Appl Microbiol Biotechnol ; 104(14): 6091-6100, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-306184

ABSTRACT

Porcine enteric coronaviruses (CoVs) cause highly contagious enteric diarrhea in suckling piglets. These COV infections are characterized by clinical signs of vomiting, watery diarrhea, dehydration, and high morbidity and mortality, resulting in significant economic losses and tremendous threats to the pig farming industry worldwide. Because the clinical manifestations of pigs infected by different CoVs are similar, it is difficult to differentiate between the specific pathogens. Effective high-throughput detection methods are powerful tools used in the prevention and control of diseases. The immune system of piglets is not well developed, so serological methods to detect antibodies against these viruses are not suitable for rapid and early detection. This paper reviews various PCR-based methods used for the rapid and efficient detection of these pathogenic CoVs in swine intestines. KEY POINTS: 1. Swine enteric coronaviruses (CoVs) emerged and reemerged in past years. 2. Enteric CoVs infect pigs at all ages with high mortality rate in suckling pigs. 3. Rapid and efficient detection methods are needed and critical for diagnosis.


Subject(s)
Coronavirus Infections/veterinary , Coronavirus/isolation & purification , Intestinal Diseases/veterinary , Polymerase Chain Reaction/methods , Swine Diseases/virology , Animals , Coronavirus/classification , Coronavirus/genetics , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Feces/virology , Intestinal Diseases/virology , Phylogeny , Swine , Swine Diseases/diagnosis
15.
Mol Biol Evol ; 37(9): 2641-2654, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-260310

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown once again that coronavirus (CoV) in animals are potential sources for epidemics in humans. Porcine deltacoronavirus (PDCoV) is an emerging enteropathogen of swine with a worldwide distribution. Here, we implemented and described an approach to analyze the epidemiology of PDCoV following its emergence in the pig population. We performed an integrated analysis of full genome sequence data from 21 newly sequenced viruses, along with comprehensive epidemiological surveillance data collected globally over the last 15 years. We found four distinct phylogenetic lineages of PDCoV, which differ in their geographic circulation patterns. Interestingly, we identified more frequent intra- and interlineage recombination and higher virus genetic diversity in the Chinese lineages compared with the USA lineage where pigs are raised in different farming systems and ecological environments. Most recombination breakpoints are located in the ORF1ab gene rather than in genes encoding structural proteins. We also identified five amino acids under positive selection in the spike protein suggesting a role for adaptive evolution. According to structural mapping, three positively selected sites are located in the N-terminal domain of the S1 subunit, which is the most likely involved in binding to a carbohydrate receptor, whereas the other two are located in or near the fusion peptide of the S2 subunit and thus might affect membrane fusion. Finally, our phylogeographic investigations highlighted notable South-North transmission as well as frequent long-distance dispersal events in China that could implicate human-mediated transmission. Our findings provide new insights into the evolution and dispersal of PDCoV that contribute to our understanding of the critical factors involved in CoVs emergence.


Subject(s)
Coronavirus Infections/veterinary , Coronavirus/genetics , Genome, Viral , Spike Glycoprotein, Coronavirus/genetics , Swine Diseases/epidemiology , Viral Proteins/genetics , Animals , Biological Evolution , China/epidemiology , Coronavirus/classification , Coronavirus/pathogenicity , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Genetic Variation , Genomics , Humans , Models, Molecular , Molecular Epidemiology , Open Reading Frames , Phylogeny , Phylogeography , Protein Structure, Secondary , Recombination, Genetic , Selection, Genetic , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Swine/virology , Swine Diseases/transmission , Swine Diseases/virology , Viral Proteins/metabolism
16.
Biomed Pharmacother ; 127: 110230, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-245718

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) has once again aroused people's concern about coronavirus. Seven human coronaviruses (HCoVs) have been discovered so far, including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU115, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 2. Existing studies show that the cardiovascular disease increased the incidence and severity of coronavirus infection. At the same time, myocardial injury caused by coronavirus infection is one of the main factors contributing to poor prognosis. In this review, the recent clinical findings about the relationship between coronaviruses and cardiovascular diseases and the underlying pathophysiological mechanisms are discussed. This review aimed to provide assistance for the prevention and treatment of COVID-19.


Subject(s)
Betacoronavirus , Cardiovascular Diseases , Coronavirus Infections , Coronavirus , Pandemics , Pneumonia, Viral , Betacoronavirus/isolation & purification , Betacoronavirus/pathogenicity , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/therapy , Cardiovascular Diseases/virology , Comorbidity , Coronavirus/classification , Coronavirus/physiology , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Humans , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Prognosis
17.
Avian Pathol ; 49(4): 313-316, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-186701

ABSTRACT

Coronaviruses (CoVs) mainly cause enteric and/or respiratory signs. Mammalian CoVs including COVID-19 (now officially named SARS-CoV-2) belong to either the Alphacoronavirus or Betacoronavirus genera. In birds, the majority of the known CoVs belong to the Gammacoronavirus genus, whilst a small number are classified as Deltacoronaviruses. Gammacoronaviruses continue to be reported in an increasing number of avian species, generally by detection of viral RNA. Apart from infectious bronchitis virus in chickens, the only avian species in which CoV has been definitively associated with disease are the turkey, pheasant and guinea fowl. Whilst there is strong evidence for recombination between gammacoronaviruses of different avian species, and between betacoronaviruses in different mammals, evidence of recombination between coronaviruses of different genera is lacking. Furthermore, the recombination of an alpha or betacoronavirus with a gammacoronavirus is extremely unlikely. For recombination to happen, the two viruses would need to be present in the same cell of the same animal at the same time, a highly unlikely scenario as they cannot replicate in the same host!


Subject(s)
Bird Diseases/virology , Coronavirus Infections/veterinary , Coronavirus/classification , Gammacoronavirus/classification , Animals , Birds , Chickens , Coronavirus Infections/virology , Galliformes , Humans , Turkeys
18.
Malays J Pathol ; 42(1): 3-11, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-159537

ABSTRACT

were identified beginning with the discovery of SARS-CoV in 2002. With the recent detection of SARS-CoV-2, there are now seven human coronaviruses. Those that cause mild diseases are the 229E, OC43, NL63 and HKU1, and the pathogenic species are SARS-CoV, MERS-CoV and SARS-CoV-2 Coronaviruses (order Nidovirales, family Coronaviridae, and subfamily Orthocoronavirinae) are spherical (125nm diameter), and enveloped with club-shaped spikes on the surface giving the appearance of a solar corona. Within the helically symmetrical nucleocapsid is the large positive sense, single stranded RNA. Of the four coronavirus genera (α,ß,γ,δ), human coronaviruses (HCoVs) are classified under α-CoV (HCoV-229E and NL63) and ß-CoV (MERS-CoV, SARS-CoV, HCoVOC43 and HCoV-HKU1). SARS-CoV-2 is a ß-CoV and shows fairly close relatedness with two bat-derived CoV-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Even so, its genome is similar to that of the typical CoVs. SARS-CoV and MERS-CoV originated in bats, and it appears to be so for SARS-CoV-2 as well. The possibility of an intermediate host facilitating the emergence of the virus in humans has already been shown with civet cats acting as intermediate hosts for SARS-CoVs, and dromedary camels for MERS-CoV. Human-to-human transmission is primarily achieved through close contact of respiratory droplets, direct contact with the infected individuals, or by contact with contaminated objects and surfaces. The coronaviral genome contains four major structural proteins: the spike (S), membrane (M), envelope (E) and the nucleocapsid (N) protein, all of which are encoded within the 3' end of the genome. The S protein mediates attachment of the virus to the host cell surface receptors resulting in fusion and subsequent viral entry. The M protein is the most abundant protein and defines the shape of the viral envelope. The E protein is the smallest of the major structural proteins and participates in viral assembly and budding. The N protein is the only one that binds to the RNA genome and is also involved in viral assembly and budding. Replication of coronaviruses begin with attachment and entry. Attachment of the virus to the host cell is initiated by interactions between the S protein and its specific receptor. Following receptor binding, the virus enters host cell cytosol via cleavage of S protein by a protease enzyme, followed by fusion of the viral and cellular membranes. The next step is the translation of the replicase gene from the virion genomic RNA and then translation and assembly of the viral replicase complexes. Following replication and subgenomic RNA synthesis, encapsidation occurs resulting in the formation of the mature virus. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/pathogenicity , Coronavirus/classification , Coronavirus/physiology , Genome, Viral , Animals , Betacoronavirus/physiology , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Humans , Nucleocapsid Proteins/genetics , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/genetics , Viral Matrix Proteins/genetics , Virus Replication
19.
Viruses ; 12(5)2020 04 30.
Article in English | MEDLINE | ID: covidwho-143828

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first occurred in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a high mortality rate, and has spread around the world. To gain an understanding of the evolution of the newly emerging SARS-CoV-2, we herein analyzed the codon usage pattern of SARS-CoV-2. For this purpose, we compared the codon usage of SARS-CoV-2 with that of other viruses belonging to the subfamily of Orthocoronavirinae. We found that SARS-CoV-2 has a high AU content that strongly influences its codon usage, which appears to be better adapted to the human host. We also studied the evolutionary pressures that influence the codon usage of five conserved coronavirus genes encoding the viral replicase, spike, envelope, membrane and nucleocapsid proteins. We found different patterns of both mutational bias and natural selection that affect the codon usage of these genes. Moreover, we show here that the two integral membrane proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their corresponding genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins (S), although they are regarded as are important targets for the development of vaccines and antiviral drugs, tend to evolve faster in comparison to the two genes mentioned above. Overall, our results suggest that the higher divergence observed for the latter three genes could represent a significant barrier in the development of antiviral therapeutics against SARS-CoV-2.


Subject(s)
Betacoronavirus/genetics , Codon , Coronavirus/genetics , Genome, Viral , Base Composition , Betacoronavirus/chemistry , Betacoronavirus/physiology , Biological Evolution , Coronavirus/classification , Genes, Viral , Host Specificity , Mutation , Phylogeny
20.
Indian J Med Res ; 151(2 & 3): 226-235, 2020.
Article in English | MEDLINE | ID: covidwho-113825

ABSTRACT

Background & objectives: Bats are considered to be the natural reservoir for many viruses, of which some are potential human pathogens. In India, an association of Pteropus medius bats with the Nipah virus was reported in the past. It is suspected that the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also has its association with bats. To assess the presence of CoVs in bats, we performed identification and characterization of bat CoV (BtCoV) in P. medius and Rousettus species from representative States in India, collected during 2018 and 2019. Methods: Representative rectal swab (RS) and throat swab specimens of Pteropus and Rousettus spp. bats were screened for CoVs using a pan-CoV reverse transcription-polymerase chain reaction (RT-PCR) targeting the RNA-dependent RNA polymerase (RdRp) gene. A single-step RT-PCR was performed on the RNA extracted from the bat specimens. Next-generation sequencing (NGS) was performed on a few representative bat specimens that were tested positive. Phylogenetic analysis was carried out on the partial sequences of RdRp gene sequences retrieved from both the bat species and complete viral genomes recovered from Rousettus spp. Results: Bat samples from the seven States were screened, and the RS specimens of eight Rousettus spp. and 21 Pteropus spp. were found positive for CoV RdRp gene. Among these, by Sanger sequencing, partial RdRp sequences could be retrieved from three Rousettus and eight Pteropus bat specimens. Phylogenetic analysis of the partial RdRp region demonstrated distinct subclustering of the BtCoV sequences retrieved from these Rousettus and Pteropus spp. bats. NGS led to the recovery of four sequences covering approximately 94.3 per cent of the whole genome of the BtCoVs from Rousettus bats. Three BtCoV sequences had 93.69 per cent identity to CoV BtRt-BetaCoV/GX2018. The fourth BtCoV sequence was 96.8 per cent identical to BtCoV HKU9-1. Interpretation & conclusions: This study was a step towards understanding the CoV circulation in Indian bats. Detection of potentially pathogenic CoVs in Indian bats stresses the need for enhanced screening for novel viruses in them. One Health approach with collaborative activities by the animal health and human health sectors in these surveillance activities shall be of use to public health. This would help in the development of diagnostic assays for novel viruses with outbreak potential and be useful in disease interventions. Proactive surveillance remains crucial for identifying the emerging novel viruses with epidemic potential and measures for risk mitigation.


Subject(s)
Chiroptera/virology , Coronavirus/classification , Coronavirus/isolation & purification , Genome, Viral , Animals , High-Throughput Nucleotide Sequencing , India , Phylogeny , Reverse Transcriptase Polymerase Chain Reaction
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