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1.
PLoS Genet ; 16(12): e1009272, 2020 12.
Article in English | MEDLINE | ID: covidwho-983907

ABSTRACT

The Betacoronaviruses comprise multiple subgenera whose members have been implicated in human disease. As with SARS, MERS and now SARS-CoV-2, the origin and emergence of new variants are often attributed to events of recombination that alter host tropism or disease severity. In most cases, recombination has been detected by searches for excessively similar genomic regions in divergent strains; however, such analyses are complicated by the high mutation rates of RNA viruses, which can produce sequence similarities in distant strains by convergent mutations. By applying a genome-wide approach that examines the source of individual polymorphisms and that can be tested against null models in which recombination is absent and homoplasies can arise only by convergent mutations, we examine the extent and limits of recombination in Betacoronaviruses. We find that recombination accounts for nearly 40% of the polymorphisms circulating in populations and that gene exchange occurs almost exclusively among strains belonging to the same subgenus. Although experimental studies have shown that recombinational exchanges occur at random along the coronaviral genome, in nature, they are vastly overrepresented in regions controlling viral interaction with host cells.


Subject(s)
Betacoronavirus/classification , Betacoronavirus/genetics , Recombination, Genetic/genetics , Spike Glycoprotein, Coronavirus/genetics , Crossing Over, Genetic/genetics , Genes, Viral/genetics , Genome, Viral/genetics , Host Specificity/genetics , Models, Genetic , Polymorphism, Genetic , /genetics , Viral Tropism/genetics
2.
Zool Res ; 41(6): 705-708, 2020 Nov 18.
Article in English | MEDLINE | ID: covidwho-982981

ABSTRACT

Since the first reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic, spreading to more than 200 countries and regions worldwide. With continued research progress and virus detection, SARS-CoV-2 genomes and sequencing data have been reported and accumulated at an unprecedented rate. To meet the need for fast analysis of these genome sequences, the National Genomics Data Center (NGDC) of the China National Center for Bioinformation (CNCB) has established an online coronavirus analysis platform, which includes de novoassembly, BLAST alignment, genome annotation, variant identification, and variant annotation modules. The online analysis platform can be freely accessed at the 2019 Novel Coronavirus Resource (2019nCoVR) (https://bigd.big.ac.cn/ncov/online/tools).


Subject(s)
Betacoronavirus/genetics , Computational Biology/methods , Coronavirus Infections/diagnosis , Genome, Viral/genetics , Genomics/methods , High-Throughput Nucleotide Sequencing/methods , Pneumonia, Viral/diagnosis , Animals , Betacoronavirus/classification , Betacoronavirus/physiology , China , Computational Biology/organization & administration , Coronavirus Infections/virology , Genetic Variation , Humans , Internet , Molecular Sequence Annotation , Pandemics , Pneumonia, Viral/virology
3.
Disaster Med Public Health Prep ; 14(3): e25-e26, 2020 06.
Article in English | MEDLINE | ID: covidwho-950866

ABSTRACT

We investigated the adoption of World Health Organization (WHO) naming of COVID-19 into the respective languages among the Group of Twenty (G20) countries, and the variation of COVID-19 naming in the Chinese language across different health authorities. On May 7, 2020, we identified the websites of the national health authorities of the G20 countries to identify naming of COVID-19 in their respective languages, and the websites of the health authorities in mainland China, Hong Kong, Macau, Taiwan and Singapore and identify their Chinese name for COVID-19. Among the G20 nations, Argentina, China, Italy, Japan, Mexico, Saudi Arabia and Turkey do not use the literal translation of COVID-19 in their official language(s) to refer to COVID-19, as they retain "novel" in the naming of this disease. China is the only G20 nation that names COVID-19 a pneumonia. Among Chinese-speaking jurisdictions, Hong Kong and Singapore governments follow the WHO's recommendation and adopt the literal translation of COVID-19 in Chinese. In contrast, mainland China, Macau, and Taiwan refer to COVID-19 as a type of pneumonia in Chinese. We urge health authorities worldwide to adopt naming in their native languages that are consistent with WHO's naming of COVID-19.


Subject(s)
Betacoronavirus/classification , Coronavirus Infections/classification , Internationality , Language , Names , Pandemics/classification , Pneumonia, Viral/classification , Humans
4.
PLoS One ; 15(11): e0240345, 2020.
Article in English | MEDLINE | ID: covidwho-917985

ABSTRACT

In late December 2019, an emerging viral infection COVID-19 was identified in Wuhan, China, and became a global pandemic. Characterization of the genetic variants of SARS-CoV-2 is crucial in following and evaluating it spread across countries. In this study, we collected and analyzed 3,067 SARS-CoV-2 genomes isolated from 55 countries during the first three months after the onset of this virus. Using comparative genomics analysis, we traced the profiles of the whole-genome mutations and compared the frequency of each mutation in the studied population. The accumulation of mutations during the epidemic period with their geographic locations was also monitored. The results showed 782 variants sites, of which 512 (65.47%) had a non-synonymous effect. Frequencies of mutated alleles revealed the presence of 68 recurrent mutations, including ten hotspot non-synonymous mutations with a prevalence higher than 0.10 in this population and distributed in six SARS-CoV-2 genes. The distribution of these recurrent mutations on the world map revealed that certain genotypes are specific to geographic locations. We also identified co-occurring mutations resulting in the presence of several haplotypes. Moreover, evolution over time has shown a mechanism of mutation co-accumulation which might affect the severity and spread of the SARS-CoV-2. The phylogentic analysis identified two major Clades C1 and C2 harboring mutations L3606F and G614D, respectively and both emerging for the first time in China. On the other hand, analysis of the selective pressure revealed the presence of negatively selected residues that could be taken into considerations as therapeutic targets. We have also created an inclusive unified database (http://covid-19.medbiotech.ma) that lists all of the genetic variants of the SARS-CoV-2 genomes found in this study with phylogeographic analysis around the world.


Subject(s)
Betacoronavirus/genetics , Genetic Variation , Genome, Viral , Betacoronavirus/classification , Betacoronavirus/isolation & purification , China , Coronavirus Infections/pathology , Coronavirus Infections/virology , Evolution, Molecular , Humans , Pandemics , Phylogeny , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Polyproteins , Protein Structure, Tertiary , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Viral Proteins/chemistry , Viral Proteins/genetics
5.
Sci Rep ; 10(1): 18289, 2020 10 26.
Article in English | MEDLINE | ID: covidwho-892042

ABSTRACT

The World Health Organization characterized COVID-19 as a pandemic in March 2020, the second pandemic of the twenty-first century. Expanding virus populations, such as that of SARS-CoV-2, accumulate a number of narrowly shared polymorphisms, imposing a confounding effect on traditional clustering methods. In this context, approaches that reduce the complexity of the sequence space occupied by the SARS-CoV-2 population are necessary for robust clustering. Here, we propose subdividing the global SARS-CoV-2 population into six well-defined subtypes and 10 poorly represented genotypes named tentative subtypes by focusing on the widely shared polymorphisms in nonstructural (nsp3, nsp4, nsp6, nsp12, nsp13 and nsp14) cistrons and structural (spike and nucleocapsid) and accessory (ORF8) genes. The six subtypes and the additional genotypes showed amino acid replacements that might have phenotypic implications. Notably, three mutations (one of them in the Spike protein) were responsible for the geographical segregation of subtypes. We hypothesize that the virus subtypes detected in this study are records of the early stages of SARS-CoV-2 diversification that were randomly sampled to compose the virus populations around the world. The genetic structure determined for the SARS-CoV-2 population provides substantial guidelines for maximizing the effectiveness of trials for testing candidate vaccines or drugs.


Subject(s)
Betacoronavirus/genetics , Polymorphism, Genetic , Betacoronavirus/classification , Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Genotype , Humans , Nucleocapsid Proteins/genetics , Pandemics , Phosphoproteins , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Spike Glycoprotein, Coronavirus/genetics , Viral Nonstructural Proteins/genetics , Viral Proteins/genetics
6.
Mol Biol Rep ; 47(11): 9207-9217, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-891912

ABSTRACT

Coronaviruses (CoVs) infect a wide range of domestic and wild mammals. These viruses have a potential and tendency to cross-species barriers and infect humans. Novel human coronavirus 2019-nCoV (hCoV-19) emerged from Wuhan, China, and has caused a global pandemic. Genomic features of SARS-CoV-2 may attribute inter-species transmission and adaptation to a novel host, and therefore is imperative to explicate the evolutionary dynamics of the viral genome and its propensity for differential host selection. We conducted an in silico analysis of all the coding gene sequences of SARS-CoV-2 strains (n = 39) originating from a range of non-human mammalian species, including pangolin, bat, dog, cat, tiger, mink, mouse, and the environmental samples such as wastewater, air and surface samples from the door handle and seafood market. Compared to the reference SARS-CoV-2 strain (MN908947; Wuhan-Hu-1), phylogenetic and comparative residue analysis revealed the circulation of three variants, including hCoV-19 virus from humans and two hCoV-19-related precursors from bats and pangolins. A lack of obvious differences as well as a maximum genetic homology among dog-, cat-, tiger-, mink-, mouse-, bat- and pangolin-derived SARS-CoV-2 sequences suggested a likely evolution of these strains from a common ancestor. Several residue substitutions were observed in the receptor-binding domain (RBD) of the spike protein, concluding a promiscuous nature of the virus for host species where genomic alternations may be required for the adaptation to novel host/s. However, such speculation needs in vitro investigations to unleash the influence of substitutions towards species-jump and disease pathogenesis.


Subject(s)
Betacoronavirus/classification , Betacoronavirus/isolation & purification , Environmental Microbiology , Animals , Betacoronavirus/genetics , Genome, Viral , Humans , Mammals/virology , Phylogeny
7.
Front Cell Infect Microbiol ; 10: 575613, 2020.
Article in English | MEDLINE | ID: covidwho-890331

ABSTRACT

Background: The ongoing pandemic of SARS-COV-2 has already infected more than eight million people worldwide. The majority of COVID-19 patients either are asymptomatic or have mild symptoms. Yet, about 15% of the cases experience severe complications and require intensive care. Factors determining disease severity are not yet fully characterized. Aim: Here, we investigated the within-host virus diversity in COVID-19 patients with different clinical manifestations. Methods: We compared SARS-COV-2 genetic diversity in 19 mild and 27 severe cases. Viral RNA was extracted from nasopharyngeal samples and sequenced using the Illumina MiSeq platform. This was followed by deep-sequencing analyses of SARS-CoV-2 genomes at both consensus and sub-consensus sequence levels. Results: Consensus sequences of all viruses were very similar, showing more than 99.8% sequence identity regardless of the disease severity. However, the sub-consensus analysis revealed significant differences in within-host diversity between mild and severe cases. Patients with severe symptoms exhibited a significantly (p-value 0.001) higher number of variants in coding and non-coding regions compared to mild cases. Analysis also revealed higher prevalence of some variants among severe cases. Most importantly, severe cases exhibited significantly higher within-host diversity (mean = 13) compared to mild cases (mean = 6). Further, higher within-host diversity was observed in patients above the age of 60 compared to the younger age group. Conclusion: These observations provided evidence that within-host diversity might play a role in the development of severe disease outcomes in COVID-19 patients; however, further investigations are required to elucidate this association.


Subject(s)
Betacoronavirus/classification , Betacoronavirus/genetics , Genetic Variation/genetics , Genome, Viral/genetics , Severity of Illness Index , Adult , Aged , Consensus Sequence/genetics , Coronavirus Infections/pathology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/pathology , RNA, Viral/genetics , Risk Factors , Sequence Analysis, RNA , Young Adult
9.
Sci Rep ; 10(1): 17766, 2020 10 20.
Article in English | MEDLINE | ID: covidwho-882928

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces severe pneumonia and is the cause of a worldwide pandemic. Coronaviruses, including SARS-CoV-2, have RNA proofreading enzymes in their genomes, resulting in fewer gene mutations than other RNA viruses. Nevertheless, variants of SARS-CoV-2 exist and may induce different symptoms; however, the factors and the impacts of these mutations are not well understood. We found that there is a bias to the mutations occurring in SARS-CoV-2 variants, with disproportionate mutation to uracil (U). These point mutations to U are mainly derived from cytosine (C), which is consistent with the substrate specificity of host RNA editing enzymes, APOBECs. We also found the point mutations which are consistent with other RNA editing enzymes, ADARs. For the C-to-U mutations, the context of the upstream uracil and downstream guanine from mutated position was found to be most prevalent. Further, the degree of increase of U in SARS-CoV-2 variants correlates with enhanced production of cytokines, such as TNF-α and IL-6, in cell lines when compared with stimulation by the ssRNA sequence of the isolated virus in Wuhan. Therefore, RNA editing is a factor for mutation bias in SARS-CoV-2 variants, which affects host inflammatory cytokines production.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/pathology , Pneumonia, Viral/pathology , APOBEC Deaminases/metabolism , Adenosine Deaminase/metabolism , Betacoronavirus/classification , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Cell Line, Tumor , Coronavirus Infections/immunology , Coronavirus Infections/virology , Humans , Interleukin-6/metabolism , Pandemics , Phylogeny , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Point Mutation , RNA Editing , Tumor Necrosis Factor-alpha/metabolism , Uracil/metabolism
10.
Sci Rep ; 10(1): 17720, 2020 10 20.
Article in English | MEDLINE | ID: covidwho-882926

ABSTRACT

International travel played a significant role in the early global spread of SARS-CoV-2. Understanding transmission patterns from different regions of the world will further inform global dynamics of the pandemic. Using data from Dubai in the United Arab Emirates (UAE), a major international travel hub in the Middle East, we establish SARS-CoV-2 full genome sequences from the index and early COVID-19 patients in the UAE. The genome sequences are analysed in the context of virus introductions, chain of transmissions, and possible links to earlier strains from other regions of the world. Phylogenetic analysis showed multiple spatiotemporal introductions of SARS-CoV-2 into the UAE from Asia, Europe, and the Middle East during the early phase of the pandemic. We also provide evidence for early community-based transmission and catalogue new mutations in SARS-CoV-2 strains in the UAE. Our findings contribute to the understanding of the global transmission network of SARS-CoV-2.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Adult , Aged , Asia/epidemiology , Betacoronavirus/classification , Betacoronavirus/isolation & purification , Child , Child, Preschool , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Europe/epidemiology , Female , Humans , Male , Middle Aged , Mutation , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Spatio-Temporal Analysis , Travel , United Arab Emirates/epidemiology , Whole Genome Sequencing , Young Adult
11.
mBio ; 11(5)2020 10 16.
Article in English | MEDLINE | ID: covidwho-873466

ABSTRACT

Recent evidence shows that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sensitive to interferons (IFNs). However, the most effective types of IFNs and the underlying antiviral effectors remain to be defined. Here, we show that zinc finger antiviral protein (ZAP), which preferentially targets CpG dinucleotides in viral RNA sequences, restricts SARS-CoV-2. We further demonstrate that ZAP and its cofactors KHNYN and TRIM25 are expressed in human lung cells. Type I, II, and III IFNs all strongly inhibited SARS-CoV-2 and further induced ZAP expression. Comprehensive sequence analyses revealed that SARS-CoV-2 and its closest relatives from horseshoe bats showed the strongest CpG suppression among all known human and bat coronaviruses, respectively. Nevertheless, endogenous ZAP expression restricted SARS-CoV-2 replication in human lung cells, particularly upon treatment with IFN-α or IFN-γ. Both the long and the short isoforms of human ZAP reduced SARS-CoV-2 RNA expression levels, but the former did so with greater efficiency. Finally, we show that the ability to restrict SARS-CoV-2 is conserved in ZAP orthologues of the reservoir bat and potential intermediate pangolin hosts of human coronaviruses. Altogether, our results show that ZAP is an important effector of the innate response against SARS-CoV-2, although this pandemic pathogen emerged from zoonosis of a coronavirus that was preadapted to the low-CpG environment in humans.IMPORTANCE Although interferons inhibit SARS-CoV-2 and have been evaluated for treatment of coronavirus disease 2019 (COVID-19), the most effective types and antiviral effectors remain to be defined. Here, we show that IFN-γ is particularly potent in restricting SARS-CoV-2 and in inducing expression of the antiviral factor ZAP in human lung cells. Knockdown experiments revealed that endogenous ZAP significantly restricts SARS-CoV-2. We further show that CpG dinucleotides which are specifically targeted by ZAP are strongly suppressed in the SARS-CoV-2 genome and that the two closest horseshoe bat relatives of SARS-CoV-2 show the lowest genomic CpG content of all coronavirus sequences available from this reservoir host. Nonetheless, both the short and long isoforms of human ZAP reduced SARS-CoV-2 RNA levels, and this activity was conserved in horseshoe bat and pangolin ZAP orthologues. Our findings indicating that type II interferon is particularly efficient against SARS-CoV-2 and that ZAP restricts this pandemic viral pathogen might promote the development of effective immune therapies against COVID-19.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/virology , CpG Islands , Pneumonia, Viral/virology , RNA-Binding Proteins/metabolism , Animals , Betacoronavirus/classification , Betacoronavirus/genetics , Betacoronavirus/metabolism , Cell Line , Coronavirus/classification , Coronavirus/genetics , Coronavirus/physiology , Gene Expression/drug effects , Genome, Viral , Humans , Interferons/pharmacology , Pandemics , Phylogeny , Protein Isoforms , RNA, Viral/genetics , RNA, Viral/metabolism , RNA-Binding Proteins/chemistry , RNA-Binding Proteins/genetics , Virus Replication/drug effects
12.
Sci Rep ; 10(1): 17492, 2020 10 15.
Article in English | MEDLINE | ID: covidwho-872738

ABSTRACT

The novel SARS-CoV-2 outbreak has swiftly spread worldwide. The rapid genome sequencing of SARS-CoV-2 strains has become a helpful tool for better understanding the genomic characteristics and origin of the virus. To obtain virus whole-genome sequences directly from clinical specimens, we performed nanopore sequencing using a modified ARTIC protocol in a portable nanopore sequencer and validated a routine 8-h workflow and a 5-h rapid pipeline. We conducted some optimization to improve the genome sequencing workflow. The sensitivity of the workflow was also tested by serially diluting RNA from clinical samples. The optimized pipeline was finally applied to obtain the whole genomes of 29 clinical specimens collected in Hangzhou from January to March 2020. In the 29 obtained complete genomes of SARS-CoV-2, 33 variations were identified and analyzed. The genomic variations and phylogenetic analysis hinted at multiple sources and different transmission patterns during the COVID-19 epidemic in Hangzhou, China. In conclusion, the genomic characteristics and origin of the virus can be quickly determined by nanopore sequencing following our workflows.


Subject(s)
Betacoronavirus/genetics , Genome, Viral , Nanopore Sequencing/methods , Adolescent , Adult , Betacoronavirus/classification , Betacoronavirus/isolation & purification , Child , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Female , Genetic Variation , Humans , Male , Middle Aged , Mutation, Missense , Pandemics , Phylogeny , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Sequence Analysis, DNA , Young Adult
13.
mBio ; 11(5)2020 10 13.
Article in English | MEDLINE | ID: covidwho-868276

ABSTRACT

Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species.IMPORTANCE The human-animal-environment interface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important aspect of the coronavirus disease 2019 (COVID-19) pandemic that requires robust One Health-based investigations. Despite this, few reports describe natural infections in animals or directly link them to human infections using genomic data. In the present study, we describe the first cases of natural SARS-CoV-2 infection in tigers and lions in the United States and provide epidemiological and genetic evidence for human-to-animal transmission of the virus. Our data show that tigers and lions were infected with different genotypes of SARS-CoV-2, indicating two independent transmission events to the animals. Importantly, infected animals shed infectious virus in respiratory secretions and feces. A better understanding of the susceptibility of animal species to SARS-CoV-2 may help to elucidate transmission mechanisms and identify potential reservoirs and sources of infection that are important in both animal and human health.


Subject(s)
Animals, Zoo/virology , Betacoronavirus/physiology , Coronavirus Infections/transmission , Coronavirus Infections/veterinary , Pandemics/veterinary , Panthera/virology , Pneumonia, Viral/transmission , Pneumonia, Viral/veterinary , Animals , Betacoronavirus/classification , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Genome, Viral/genetics , Haplotypes , Humans , New York City/epidemiology , One Health , Phylogeny , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Zoonoses/epidemiology , Zoonoses/transmission , Zoonoses/virology
14.
J Clin Microbiol ; 58(10)2020 09 22.
Article in English | MEDLINE | ID: covidwho-858045

ABSTRACT

Control of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires accurate laboratory testing to identify infected individuals while also clearing essential staff to continue to work. At the current time, a number of quantitative real-time PCR (qRT-PCR) assays have been developed to identify SARS-CoV-2, targeting multiple positions in the viral genome. While the mutation rate of SARS-CoV-2 is moderate, given the large number of transmission chains, it is prudent to monitor circulating viruses for variants that might compromise these assays. Here, we report the identification of a C-to-U transition at position 26340 of the SARS-CoV-2 genome that is associated with failure of the cobas SARS-CoV-2 E gene qRT-PCR in eight patients. As the cobas SARS-CoV-2 assay targets two positions in the genome, the individuals carrying this variant were still called SARS-CoV-2 positive. Whole-genome sequencing of SARS-CoV-2 showed all to carry closely related viruses. Examination of viral genomes deposited on GISAID showed this mutation has arisen independently at least four times. This work highlights the necessity of monitoring SARS-CoV-2 for the emergence of single-nucleotide polymorphisms that might adversely affect RT-PCRs used in diagnostics. Additionally, it argues that two regions in SARS-CoV-2 should be targeted to avoid false negatives.


Subject(s)
Betacoronavirus/genetics , Viral Envelope Proteins/genetics , Betacoronavirus/classification , Betacoronavirus/isolation & purification , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Databases, Genetic , False Negative Reactions , Genome, Viral/genetics , Humans , Molecular Diagnostic Techniques , Mutation , Phylogeny , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction
15.
PLoS Negl Trop Dis ; 14(10): e0008570, 2020 10.
Article in English | MEDLINE | ID: covidwho-841536

ABSTRACT

Little is known about the SARS-CoV-2 contamination of environmental surfaces and air in non-health care settings among COVID-19 cases. We explored the SARS-CoV-2 contamination of environmental surfaces and air by collecting air and swabbing environmental surfaces among 39 COVID-19 cases in Guangzhou, China. The specimens were tested on RT-PCR. The information collected for COVID-19 cases included basic demographic, clinical severity, symptoms at onset, radiological testing, laboratory testing and hospital admission. A total of 641 environmental surfaces and air specimens were collected among 39 COVID-19 cases before disinfection. Among them, 20 specimens (20/641, 3.1%) were tested positive from 9 COVID-19 cases (9/39, 23.1%), with 5 (5/101, 5.0%) positive specimens from 3 asymptomatic cases, 5 (5/220, 2.3%) from 3 mild cases, and 10 (10/374, 2.7%) from 3 moderate cases. All positive specimens were collected within 3 days after diagnosis, and 10 (10/42, 23.8%) were found in toilet (5 on toilet bowl, 4 on sink/faucet/shower, 1 on floor drain), 4 (4/21, 19.0%) in anteroom (2 on water dispenser/cup/bottle, 1 on chair/table, 1 on TV remote), 1 (1/8, 12.5%) in kitchen (1 on dining-table), 1 (1/18, 5.6%) in bedroom (1 on bed/sheet pillow/bedside table), 1 (1/5, 20.0%) in car (1 on steering wheel/seat/handlebar) and 3 (3/20, 21.4%) on door knobs. Air specimens in room (0/10, 0.0%) and car (0/1, 0.0%) were all negative. SARS-CoV-2 was found on environmental surfaces especially in toilet, and may survive for several days. We provided evidence of potential for SARS-CoV-2 transmission through contamination of environmental surfaces.


Subject(s)
Air Microbiology , Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Equipment Contamination/statistics & numerical data , Pneumonia, Viral/virology , Adolescent , Adult , Aged , Betacoronavirus/classification , Betacoronavirus/genetics , China/epidemiology , Coronavirus Infections/epidemiology , Environmental Microbiology , Female , Household Articles , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Young Adult
16.
Sci Rep ; 10(1): 16471, 2020 10 05.
Article in English | MEDLINE | ID: covidwho-834901

ABSTRACT

SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.


Subject(s)
Peptidyl-Dipeptidase A/chemistry , Phylogeny , Spike Glycoprotein, Coronavirus/chemistry , Animals , Betacoronavirus/classification , Betacoronavirus/genetics , Humans , Mammals , Molecular Docking Simulation , Mutation , Peptidyl-Dipeptidase A/classification , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Protein Binding , Spike Glycoprotein, Coronavirus/metabolism
17.
Medwave ; 20(8)30-09-2020.
Article in English, Spanish | LILACS (Americas) | ID: covidwho-814798

ABSTRACT

El síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2) es responsable de la enfermedad denominada COVID-19 (acrónimo del inglés Coronavirus Disease-2019). Esta enfermedad fue detectada inicialmente en la ciudad de Wuhan, China en diciembre de 2019. Las personas contagiadas con COVID-19 presentan síntomas variados, dependiendo de su estado de salud y edad. Los síntomas más comunes son fiebre, tos, mialgia, fatiga, odinofagia y disnea. También se ha observado que en algunos pacientes, la infección es asintomática. Los adultos mayores de 60 años infectados son el grupo de pacientes más susceptibles a desarrollar estados severos de COVID-19 y se presenta comorbilidad en presencia de enfermedades crónicas. Por otra parte, también es importante disponer de pruebas que permitan detectar al SARS-COV-2 y seguir la evolución de COVID-19 de forma rápida, confiable y barata. Para lograr esto, existen pruebas de reacción en cadena de la polimerasa de transcripción inversa en tiempo real (RT-PCR), de amplificación isotérmica de ácido nucleico y de inmunoestimulación enzimática. Actualmente, no existen tratamientos para la prevención del contagio y combatir los efectos del virus en la salud humana. Sin embargo, en el mundo hay grupos de investigación que están realizando pruebas in vitro, in vivo e in silico para encontrar fármacos que sean capaces de prevenir y/o controlar la infección en humanos con SARS-CoV-2. La cloroquina, hidroxicloroquina, remdesivir, interferon-2b y oseltamivir son algunas de las opciones farmacológicas que están siendo evaluadas en pruebas clínicas para la profilaxis de COVID-19. El objetivo de la presente revisión consiste en establecer un marco de referencia de la clasificación taxonómica del SARS-CoV-2 y la relación que guardan con otros coronavirus, así como su estructura y forma de propagarse en el ser humano. También se presentan las características y síntomas de pacientes con COVID-19, los métodos de detección y potenciales tratamientos.


Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19 (Coronavirus disease 2019). This disease was detected in the city of Wuhan in China in December 2019. People infected with COVID-19 shows varying manifestations, depending on their health and age. The most common symptoms are fever, cough, myalgia, fatigue, odynophagia, and dyspnea. Infected adults older 60 years of age are the group of patients most susceptible to severe COVID-19 states and present comor-bidity in the presence of chronic diseases. On the other hand, it is also essential to have tests to detect SARS-COV-2 in people and follow the evolution of COVID-19 quickly, reliably, and cheap. To achieve this, there are real-time reverse transcription pol-ymerase chain reaction (RT-PCR) tests, isothermal nucleic acid amplification, and enzyme immunostimulation. Currently, there are no drug treatments to prevent infection and to combat the virus's effects. However, different research groups that are conduct-ing in vitro, in vivo, and in silico tests to find drugs able to provide an immune response and to control infection in humans with SARS-CoV-2. Chloroquine, hydroxychloroquine, remdesivir, interferon-2b, and oseltamivir are some pharmacological options evaluated in clinical trials for prophylaxis of COVID-19. The purpose of this review is to establish a reference framework for taxonomic classification of SARS-CoV-2 and the relationship they have with other CoVs, as well as their structure and propaga-tion pathways in humans. The characteristics and symptoms presented by patients with COVID-19, the detection methods, and possible treatments are also presented.


Subject(s)
Humans , Pneumonia, Viral/epidemiology , Coronavirus Infections/epidemiology , Clinical Laboratory Techniques , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Risk Factors , Age Factors , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Pandemics , Betacoronavirus/isolation & purification , Betacoronavirus/classification
18.
J Virol ; 94(18)2020 08 31.
Article in English | MEDLINE | ID: covidwho-803471

ABSTRACT

The COVID-19 pandemic has caused an unprecedented global public health and economic crisis. The origin and emergence of its causal agent, SARS-CoV-2, in the human population remains mysterious, although bat and pangolin were proposed to be the natural reservoirs. Strikingly, unlike the SARS-CoV-2-like coronaviruses (CoVs) identified in bats and pangolins, SARS-CoV-2 harbors a polybasic furin cleavage site in its spike (S) glycoprotein. SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) as its receptor to infect cells. Receptor recognition by the S protein is the major determinant of host range, tissue tropism, and pathogenesis of coronaviruses. In an effort to search for the potential intermediate or amplifying animal hosts of SARS-CoV-2, we examined receptor activity of ACE2 from 14 mammal species and found that ACE2s from multiple species can support the infectious entry of lentiviral particles pseudotyped with the wild-type or furin cleavage site-deficient S protein of SARS-CoV-2. ACE2 of human/rhesus monkey and rat/mouse exhibited the highest and lowest receptor activities, respectively. Among the remaining species, ACE2s from rabbit and pangolin strongly bound to the S1 subunit of SARS-CoV-2 S protein and efficiently supported the pseudotyped virus infection. These findings have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models.IMPORTANCE SARS-CoV-2 uses human ACE2 as a primary receptor for host cell entry. Viral entry mediated by the interaction of ACE2 with spike protein largely determines host range and is the major constraint to interspecies transmission. We examined the receptor activity of 14 ACE2 orthologs and found that wild-type and mutant SARS-CoV-2 lacking the furin cleavage site in S protein could utilize ACE2 from a broad range of animal species to enter host cells. These results have important implications in the natural hosts, interspecies transmission, animal models, and molecular basis of receptor binding for SARS-CoV-2.


Subject(s)
Animal Diseases/metabolism , Animal Diseases/virology , Betacoronavirus/physiology , Coronavirus Infections/veterinary , Pandemics/veterinary , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/veterinary , Receptors, Virus/metabolism , Amino Acid Sequence , Animals , Betacoronavirus/classification , Cell Line , Host Specificity , Humans , Models, Molecular , Mutation , Peptidyl-Dipeptidase A/chemistry , Phylogeny , Protein Binding , Protein Domains , Proteolysis , Receptors, Virus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Structure-Activity Relationship , Viral Tropism , Virus Internalization
20.
J Transl Med ; 18(1): 358, 2020 09 21.
Article in English | MEDLINE | ID: covidwho-781481

ABSTRACT

COVID-19 caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan (Hubei province, China) during late 2019. It has spread across the globe affecting nearly 21 million people with a toll of 0.75 million deaths and restricting the movement of most of the world population during the past 6 months. COVID-19 became the leading health, economic, and humanitarian challenge of the twenty-first century. In addition to the considerable COVID-19 cases, hospitalizations, and deaths in humans, several cases of SARS-CoV-2 infections in animal hosts (dog, cat, tiger, lion, and mink) have been reported. Thus, the concern of pet owners is increasing. Moreover, the dynamics of the disease requires further explanation, mainly concerning the transmission of the virus from humans to animals and vice versa. Therefore, this study aimed to gather information about the reported cases of COVID-19 transmission in animals through a literary review of works published in scientific journals and perform genomic and phylogenetic analyses of SARS-CoV-2 isolated from animal hosts. Although many instances of transmission of the SARS-CoV-2 have been reported, caution and further studies are necessary to avoid the occurrence of maltreatment in animals, and to achieve a better understanding of the dynamics of the disease in the environment, humans, and animals. Future research in the animal-human interface can help formulate and implement preventive measures to combat the further transmission of COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/veterinary , Pandemics/veterinary , Pneumonia, Viral/veterinary , Zoonoses/transmission , Animal Husbandry , Animals , Betacoronavirus/classification , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , Cats , Coronavirus/classification , Coronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Disease Reservoirs/veterinary , Disease Reservoirs/virology , Dogs , Genome, Viral , Humans , Mink/virology , Netherlands/epidemiology , Occupational Exposure , Pets/virology , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Spike Glycoprotein, Coronavirus/genetics , Translational Medical Research , Zoonoses/epidemiology
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