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1.
Sci Rep ; 11(1): 17365, 2021 08 30.
Article in English | MEDLINE | ID: covidwho-1379334

ABSTRACT

The SARS-CoV-2 pandemic prompts evaluation of recombination in human coronavirus (hCoV) evolution. We undertook recombination analyses of 158,118 public seasonal hCoV, SARS-CoV-1, SARS-CoV-2 and MERS-CoV genome sequences using the RDP4 software. We found moderate evidence for 8 SARS-CoV-2 recombination events, two of which involved the spike gene, and low evidence for one SARS-CoV-1 recombination event. Within MERS-CoV, 229E, OC43, NL63 and HKU1 datasets, we noted 7, 1, 9, 14, and 1 high-confidence recombination events, respectively. There was propensity for recombination breakpoints in the non-ORF1 region of the genome containing structural genes, and recombination severely skewed the temporal structure of these data, especially for NL63 and OC43. Bayesian time-scaled analyses on recombinant-free data indicated the sampled diversity of seasonal CoVs emerged in the last 70 years, with 229E displaying continuous lineage replacements. These findings emphasize the importance of genomic based surveillance to detect recombination in SARS-CoV-2, particularly if recombination may lead to immune evasion.


Subject(s)
Middle East Respiratory Syndrome Coronavirus/genetics , Recombination, Genetic , SARS Virus/genetics , SARS-CoV-2/genetics , Bayes Theorem , Databases, Genetic , Genome, Viral , Humans , Immune Evasion , Middle East Respiratory Syndrome Coronavirus/classification , SARS Virus/classification , SARS-CoV-2/classification , Spike Glycoprotein, Coronavirus/genetics , Viral Nonstructural Proteins/genetics
2.
PLoS One ; 16(6): e0252534, 2021.
Article in English | MEDLINE | ID: covidwho-1270459

ABSTRACT

Many recent disease outbreaks in humans had a zoonotic virus etiology. Bats in particular have been recognized as reservoirs to a large variety of viruses with the potential to cross-species transmission. In order to assess the risk of bats in Switzerland for such transmissions, we determined the virome of tissue and fecal samples of 14 native and 4 migrating bat species. In total, sequences belonging to 39 different virus families, 16 of which are known to infect vertebrates, were detected. Contigs of coronaviruses, adenoviruses, hepeviruses, rotaviruses A and H, and parvoviruses with potential zoonotic risk were characterized in more detail. Most interestingly, in a ground stool sample of a Vespertilio murinus colony an almost complete genome of a Middle East respiratory syndrome-related coronavirus (MERS-CoV) was detected by Next generation sequencing and confirmed by PCR. In conclusion, bats in Switzerland naturally harbour many different viruses. Metagenomic analyses of non-invasive samples like ground stool may support effective surveillance and early detection of viral zoonoses.


Subject(s)
Chiroptera/virology , Feces/virology , Metagenomics/methods , Virome/genetics , Viruses/genetics , Zoonoses/virology , Adenoviridae/classification , Adenoviridae/genetics , Animals , Chiroptera/classification , Disease Reservoirs/virology , Genetic Variation , Genome, Viral/genetics , Hepevirus/classification , Hepevirus/genetics , Humans , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/genetics , Phylogeny , Rotavirus/classification , Rotavirus/genetics , Sequence Analysis, DNA/methods , Switzerland , Viruses/classification
3.
Comput Med Imaging Graph ; 90: 101921, 2021 06.
Article in English | MEDLINE | ID: covidwho-1201523

ABSTRACT

Novel corona-virus (nCOV) has been declared as a pandemic that started from the city Wuhan of China. This deadly virus is infecting people rapidly and has targeted 4.93 million people across the world, with 227 K people being infected only in Italy. Cases of nCOV are quickly increasing whereas the number of nCOV test kits available in hospitals are limited. Under these conditions, an automated system for the classification of patients into nCOV positive and negative cases, is a much needed tool against the pandemic, helping in a selective use of the limited number of test kits. In this research, Convolutional Neural Network-based models (one block VGG, two block VGG, three block VGG, four block VGG, LetNet-5, AlexNet, and Resnet-50) have been employed for the detection of Corona-virus and SARS_MERS infected patients, distinguishing them from the healthy subjects, using lung X-ray scans, which has proven to be a challenging task, due to overlapping characteristics of different corona virus types. Furthermore, LSTM model has been used for time series forecasting of nCOV cases, in the following 10 days, in Italy. The evaluation results obtained, proved that the VGG1 model distinguishes the three classes at an accuracy of almost 91%, as compared to other models, whereas the approach based on the LSTM predicts the number of nCOV cases with 99% accuracy.


Subject(s)
Betacoronavirus/classification , Deep Learning , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , Humans , Middle East Respiratory Syndrome Coronavirus/classification , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , SARS-CoV-2/classification
4.
J Mol Med (Berl) ; 99(1): 93-106, 2021 01.
Article in English | MEDLINE | ID: covidwho-956167

ABSTRACT

In humans, coronaviruses can cause infections of the respiratory system, with damage of varying severity depending on the virus examined: ranging from mild-to-moderate upper respiratory tract diseases, such as the common cold, pneumonia, severe acute respiratory syndrome, kidney failure, and even death. Human coronaviruses known to date, common throughout the world, are seven. The most common-and least harmful-ones were discovered in the 1960s and cause a common cold. Others, more dangerous, identified in the early 2000s and cause more severe respiratory tract infections. Among these the SARS-CoV, isolated in 2003 and responsible for the severe acute respiratory syndrome (the so-called SARS), which appeared in China in November 2002, the coronavirus 2012 (2012-nCoV) cause of the Middle Eastern respiratory syndrome (MERS) from coronavirus, which exploded in June 2012 in Saudi Arabia, and actually SARS-CoV-2. On December 31, 2019, a new coronavirus strain was reported in Wuhan, China, identified as a new coronavirus beta strain ß-CoV from group 2B, with a genetic similarity of approximately 70% to SARS-CoV, the virus responsible of SARS. In the first half of February, the International Committee on Taxonomy of Viruses (ICTV), in charge of the designation and naming of the viruses (i.e., species, genus, family, etc.), thus definitively named the new coronavirus as SARS-CoV-2. This article highlights the main knowledge we have about the biomolecular and pathophysiologic mechanisms of SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/genetics , COVID-19/metabolism , COVID-19/virology , China , Coronavirus Infections/classification , Coronavirus Infections/genetics , Coronavirus Infections/metabolism , Humans , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/metabolism , SARS Virus/classification , SARS Virus/genetics , SARS Virus/metabolism , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/metabolism
5.
Emerg Infect Dis ; 26(12): 3089-3091, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-938339

ABSTRACT

We detected Middle East respiratory syndrome coronavirus (MERS-CoV) RNA in 305/1,131 (27%) camels tested at an abattoir in Al Hasa, Eastern Province, Saudi Arabia, during January 2016-March 2018. We characterized 48 full-length MERS-CoV genomes and noted the viruses clustered in MERS-CoV lineage 5 clade B.


Subject(s)
Abattoirs , Camelus , Coronavirus Infections/veterinary , Middle East Respiratory Syndrome Coronavirus/genetics , Phylogeny , Aging , Animals , Antibodies, Viral/analysis , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Male , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/isolation & purification , RNA, Viral/analysis , Saudi Arabia/epidemiology
6.
Genomics ; 113(1 Pt 2): 778-784, 2021 01.
Article in English | MEDLINE | ID: covidwho-867194

ABSTRACT

The coronavirus pandemic became a major risk in global public health. The outbreak is caused by SARS-CoV-2, a member of the coronavirus family. Though the images of the virus are familiar to us, in the present study, an attempt is made to hear the coronavirus by translating its protein spike into audio sequences. The musical features such as pitch, timbre, volume and duration are mapped based on the coronavirus protein sequence. Three different viruses Influenza, Ebola and Coronavirus were studied and compared through their auditory virus sequences by implementing Haar wavelet transform. The sonification of the coronavirus benefits in understanding the protein structures by enhancing the hidden features. Further, it makes a clear difference in the representation of coronavirus compared with other viruses, which will help in various research works related to virus sequence. This evolves as a simplified and novel way of representing the conventional computational methods.


Subject(s)
Algorithms , COVID-19/virology , Genome, Viral , Music , SARS-CoV-2/classification , SARS-CoV-2/genetics , Wavelet Analysis , Amino Acid Sequence , Cluster Analysis , Coronavirus/classification , Coronavirus/genetics , Ebolavirus/classification , Ebolavirus/genetics , Humans , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/genetics , Orthomyxoviridae/classification , Orthomyxoviridae/genetics , Pandemics , RNA, Viral/genetics , SARS Virus/classification , SARS Virus/genetics , Viral Proteins/genetics
7.
Epidemiol Infect ; 148: e247, 2020 10 14.
Article in English | MEDLINE | ID: covidwho-867335

ABSTRACT

Dromedary camels remain the currently identified reservoir for the Middle East respiratory syndrome coronavirus (MERS-CoV). The virus is released in the secretions of the infected camels, especially the nasal tract. The virus shedding curve through the nasal secretions was studied. Although human transmission of the virus through the respiratory tract of close contact people with dromedary reported previously, the exact mechanism of transmission is still largely unknown. The main goal of this study was to check the possibility of MERS-CoV shedding in the exhaled air of the infected camels. To achieve this goal, we conducted a follow-up study in one of the dromedary camel herds, December 2018-April 2019. We tested nasal swabs, breath samples from animals within this herd by the real-time PCR. Our results showed that some of the tested nasal swabs and breath were positive from 24 March 2019 until 7 April 2019. The phylogenetic analysis of the obtained S and N gene sequences revealed the detected viruses are clustering together with some human and camel samples from the eastern region, especially from Al-Hufuf city, as well as some samples from Qatar and Jordon. These results are clearly showing the possibility of shedding of the virus in the breath of the infected camels. This could explain, at least in part, the mechanism of transmission of MERS-CoV from animals to humans. This study is confirming the shedding of MERS-CoV in the exhaled air of the infected camels. Further studies are needed for a better understanding of the MERS-CoV.


Subject(s)
Camelus/virology , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Animals , Breath Tests , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/genetics , Nose/virology , Phylogeny , RNA, Viral/analysis , Virus Shedding
8.
J Virol ; 94(15)2020 07 16.
Article in English | MEDLINE | ID: covidwho-762192

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory disease in humans. MERS-CoV strains from early epidemic clade A and contemporary epidemic clade B have not been phenotypically characterized to compare their abilities to infect cells and mice. We isolated the clade B MERS-CoV ChinaGD01 strain from a patient infected during the South Korean MERS outbreak in 2015 and compared the phylogenetics and pathogenicity of MERS-CoV EMC/2012 (clade A) and ChinaGD01 (clade B) in vitro and in vivo Genome alignment analysis showed that most clade-specific mutations occurred in the orf1ab gene, including mutations that were predicted to be potential glycosylation sites. Minor differences in viral growth but no significant differences in plaque size or sensitivity to beta interferon (IFN-ß) were detected between these two viruses in vitro ChinaGD01 virus infection induced more weight loss and inflammatory cytokine production in human DPP4-transduced mice. Viral titers were higher in the lungs of ChinaGD01-infected mice than with EMC/2012 infection. Decreased virus-specific CD4+ and CD8+ T cell numbers were detected in the lungs of ChinaGD01-infected mice. In conclusion, MERS-CoV evolution induced changes to reshape its pathogenicity and virulence in vitro and in vivo and to evade adaptive immune response to hinder viral clearance.IMPORTANCE MERS-CoV is an important emerging pathogen and causes severe respiratory infection in humans. MERS-CoV strains from early epidemic clade A and contemporary epidemic clade B have not been phenotypically characterized to compare their abilities to infect cells and mice. In this study, we showed that a clade B virus ChinaGD01 strain caused more severe disease in mice, with delayed viral clearance, increased inflammatory cytokines, and decreased antiviral T cell responses, than the early clade A virus EMC/2012. Given the differences in pathogenicity of different clades of MERS-CoV, periodic assessment of currently circulating MERS-CoV is needed to monitor potential severity of zoonotic disease.


Subject(s)
Coronavirus Infections/virology , Genotype , Host-Pathogen Interactions , Middle East Respiratory Syndrome Coronavirus/physiology , Adult , Animals , Disease Models, Animal , Genome, Viral , Host-Pathogen Interactions/immunology , Humans , Interferon Type I/pharmacology , Male , Mice , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Phylogeny , RNA, Viral , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Virulence , Virus Replication/drug effects , Virus Replication/genetics , Whole Genome Sequencing
9.
Open Vet J ; 10(2): 164-177, 2020 08.
Article in English | MEDLINE | ID: covidwho-724486

ABSTRACT

Viruses are having great time as they seem to have bogged humans down. Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and novel coronavirus (COVID-19) are the three major coronaviruses of present-day global human and animal health concern. COVID-19 caused by SARS-CoV-2 is identified as the newest disease, presumably of bat origin. Different theories on the evolution of viruses are in circulation, yet there is no denying the fact that the animal source is the skeleton. The whole world is witnessing the terror of the COVID-19 pandemic that is following the same path of SARS and MERS, and seems to be more severe. In addition to humans, several species of animals are reported to have been infected with these life-threatening viruses. The possible routes of transmission and their zoonotic potentialities are the subjects of intense research. This review article aims to overview the link of all these three deadly coronaviruses among animals along with their phylogenic evolution and cross-species transmission. This is essential since animals as pets or food are said to pose some risk, and their better understanding is a must in order to prepare a possible plan for future havoc in both human and animal health. Although COVID-19 is causing a human health hazard globally, its reporting in animals are limited compared to SARS and MERS. Non-human primates and carnivores are most susceptible to SARS-coronavirus and SARS-CoV-2, respectively, whereas the dromedary camel is susceptible to MERS-coronavirus. Phylogenetically, the trio viruses are reported to have originated from bats and have special capacity to undergo mutation and genomic recombination in order to infect humans through its reservoir or replication host. However, it is difficult to analyze how the genomic pattern of coronaviruses occurs. Thus, increased possibility of new virus-variants infecting humans and animals in the upcoming days seems to be the biggest challenge for the future of the world. One health approach is portrayed as our best way ahead, and understanding the animal dimension will go a long way in formulating such preparedness plans.


Subject(s)
Betacoronavirus/classification , Coronavirus Infections/veterinary , Middle East Respiratory Syndrome Coronavirus/classification , Pandemics/veterinary , Pneumonia, Viral/veterinary , SARS Virus/classification , Severe Acute Respiratory Syndrome/veterinary , Animals , Animals, Wild , Betacoronavirus/genetics , COVID-19 , Camelids, New World/virology , Camelus/virology , Cats , Chiroptera/virology , Coronavirus Infections/immunology , Coronavirus Infections/transmission , Disease Susceptibility/veterinary , Dogs , Eutheria/virology , Ferrets/virology , Humans , Lions/virology , Middle East Respiratory Syndrome Coronavirus/genetics , Phylogeny , Pneumonia, Viral/immunology , Pneumonia, Viral/transmission , Primates/virology , Raccoon Dogs/virology , SARS Virus/genetics , SARS-CoV-2 , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/transmission , Snakes/virology , Tigers/virology , Viverridae/virology
10.
Infect Genet Evol ; 84: 104440, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-621792

ABSTRACT

SARS-CoV-2, a new coronavirus strain responsible for COVID-19, has emerged in Wuhan City, China, and continuing its global pandemic nature. The availability of the complete gene sequences of the virus helps to know about the origin and molecular characteristics of this virus. In the present study, we performed bioinformatic analysis of the available gene sequence data of SARS-CoV-2 for the understanding of evolution and molecular characteristics and immunogenic resemblance of the circulating viruses. Phylogenetic analysis was performed for four types of representative viral proteins (spike, membrane, envelope and nucleoprotein) of SARS-CoV-2, HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HKU1, MERS-CoV, HKU4, HKU5 and BufCoV-HKU26. The findings demonstrated that SARS-CoV-2 exhibited convergent evolutionary relation with previously reported SARS-CoV. It was also depicted that SARS-CoV-2 proteins were highly similar and identical to SARS-CoV proteins, though proteins from other coronaviruses showed a lower level of resemblance. The cross-checked conservancy analysis of SARS-CoV-2 antigenic epitopes showed significant conservancy with antigenic epitopes derived from SARS-CoV. Descriptive epidemiological analysis on several epidemiological indices was performed on available epidemiological outbreak information from several open databases on COVID-19 (SARS-CoV-2). Satellite-derived imaging data have been employed to understand the role of temperature in the environmental persistence of the virus. Findings of the descriptive analysis were used to describe the global impact of newly emerged SARS-CoV-2, and the risk of an epidemic in Bangladesh.


Subject(s)
Antigens, Viral/genetics , Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Genome, Viral , Pandemics , Pneumonia, Viral/epidemiology , SARS Virus/genetics , Spike Glycoprotein, Coronavirus/chemistry , Alphacoronavirus/classification , Alphacoronavirus/genetics , Alphacoronavirus/metabolism , Amino Acid Sequence , Animals , Antigens, Viral/chemistry , Antigens, Viral/metabolism , Bangladesh/epidemiology , Base Sequence , Betacoronavirus/classification , Betacoronavirus/metabolism , Binding Sites , COVID-19 , Chiroptera/virology , Computational Biology , Coronavirus 229E, Human/classification , Coronavirus 229E, Human/genetics , Coronavirus 229E, Human/metabolism , Coronavirus Infections/virology , Coronavirus NL63, Human/classification , Coronavirus NL63, Human/genetics , Coronavirus NL63, Human/metabolism , Coronavirus OC43, Human/classification , Coronavirus OC43, Human/genetics , Coronavirus OC43, Human/metabolism , Humans , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/metabolism , Models, Molecular , Mutation , Nucleoproteins/chemistry , Nucleoproteins/genetics , Nucleoproteins/metabolism , Phylogeny , Pneumonia, Viral/virology , Protein Binding , Protein Interaction Domains and Motifs , SARS Virus/classification , SARS Virus/metabolism , SARS-CoV-2 , Sequence Alignment , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Viral Envelope Proteins/chemistry , Viral Envelope Proteins/genetics , Viral Envelope Proteins/metabolism
11.
Proc Natl Acad Sci U S A ; 117(26): 15193-15199, 2020 06 30.
Article in English | MEDLINE | ID: covidwho-595720

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an immediate, major threat to public health across the globe. Here we report an in-depth molecular analysis to reconstruct the evolutionary origins of the enhanced pathogenicity of SARS-CoV-2 and other coronaviruses that are severe human pathogens. Using integrated comparative genomics and machine learning techniques, we identify key genomic features that differentiate SARS-CoV-2 and the viruses behind the two previous deadly coronavirus outbreaks, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), from less pathogenic coronaviruses. These features include enhancement of the nuclear localization signals in the nucleocapsid protein and distinct inserts in the spike glycoprotein that appear to be associated with high case fatality rate of these coronaviruses as well as the host switch from animals to humans. The identified features could be crucial contributors to coronavirus pathogenicity and possible targets for diagnostics, prognostication, and interventions.


Subject(s)
Betacoronavirus/genetics , Evolution, Molecular , Genome, Viral , Nucleocapsid Proteins/genetics , Spike Glycoprotein, Coronavirus/genetics , Animals , Betacoronavirus/classification , Betacoronavirus/pathogenicity , Host Specificity , Humans , Machine Learning , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Mutagenesis, Insertional , Nuclear Localization Signals/genetics , Nucleocapsid Proteins/chemistry , Phylogeny , SARS-CoV-2 , Sequence Homology , Spike Glycoprotein, Coronavirus/chemistry , Virulence/genetics
12.
Viruses ; 12(6)2020 06 03.
Article in English | MEDLINE | ID: covidwho-532726

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans; the second-largest and most deadly outbreak to date occurred in Saudi Arabia. The dromedary camel is considered a possible host of the virus and also to act as a reservoir, transmitting the virus to humans. Here, we studied evolutionary relationships for 31 complete genomes of betacoronaviruses, including eight newly sequenced MERS-CoV genomes isolated from dromedary camels in Saudi Arabia. Through bioinformatics tools, we also used available sequences and 3D structure of MERS-CoV spike glycoprotein to predict MERS-CoV epitopes and assess antibody binding affinity. Phylogenetic analysis showed the eight new sequences have close relationships with existing strains detected in camels and humans in Arabian Gulf countries. The 2019-nCov strain appears to have higher homology to both bat coronavirus and SARS-CoV than to MERS-CoV strains. The spike protein tree exhibited clustering of MERS-CoV sequences similar to the complete genome tree, except for one sequence from Qatar (KF961222). B cell epitope analysis determined that the MERS-CoV spike protein has 24 total discontinuous regions from which just six epitopes were selected with score values of >80%. Our results suggest that the virus circulates by way of camels crossing the borders of Arabian Gulf countries. This study contributes to finding more effective vaccines in order to provide long-term protection against MERS-CoV and identifying neutralizing antibodies.


Subject(s)
Camelus/virology , Coronavirus Infections/virology , Middle East Respiratory Syndrome Coronavirus/genetics , Spike Glycoprotein, Coronavirus/genetics , Amino Acid Sequence , Animals , Betacoronavirus/classification , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Biological Evolution , DNA, Complementary/chemistry , DNA, Viral/chemistry , Epitopes/analysis , Epitopes/chemistry , Epitopes/genetics , Gene Library , Humans , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Phylogeny , RNA, Viral/analysis , RNA, Viral/chemistry , RNA, Viral/isolation & purification , Saudi Arabia
13.
J Med Virol ; 92(6): 660-666, 2020 06.
Article in English | MEDLINE | ID: covidwho-7544

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease with fatal outcomes. In this study, a fundamental knowledge gap question is to be resolved by evaluating the differences in biological and pathogenic aspects of SARS-CoV-2 and the changes in SARS-CoV-2 in comparison with the two prior major COV epidemics, SARS and Middle East respiratory syndrome (MERS) coronaviruses. METHODS: The genome composition, nucleotide analysis, codon usage indices, relative synonymous codons usage, and effective number of codons (ENc) were analyzed in the four structural genes; Spike (S), Envelope (E), membrane (M), and Nucleocapsid (N) genes, and two of the most important nonstructural genes comprising RNA-dependent RNA polymerase and main protease (Mpro) of SARS-CoV-2, Beta-CoV from pangolins, bat SARS, MERS, and SARS CoVs. RESULTS: SARS-CoV-2 prefers pyrimidine rich codons to purines. Most high-frequency codons were ending with A or T, while the low frequency and rare codons were ending with G or C. SARS-CoV-2 structural proteins showed 5 to 20 lower ENc values, compared with SARS, bat SARS, and MERS CoVs. This implies higher codon bias and higher gene expression efficiency of SARS-CoV-2 structural proteins. SARS-CoV-2 encoded the highest number of over-biased and negatively biased codons. Pangolin Beta-CoV showed little differences with SARS-CoV-2 ENc values, compared with SARS, bat SARS, and MERS CoV. CONCLUSION: Extreme bias and lower ENc values of SARS-CoV-2, especially in Spike, Envelope, and Mpro genes, are suggestive for higher gene expression efficiency, compared with SARS, bat SARS, and MERS CoVs.


Subject(s)
Betacoronavirus/genetics , Cysteine Endopeptidases/genetics , Middle East Respiratory Syndrome Coronavirus/genetics , Nucleocapsid Proteins/genetics , RNA-Dependent RNA Polymerase/genetics , SARS Virus/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/genetics , Viral Nonstructural Proteins/genetics , Animals , Base Sequence , Betacoronavirus/classification , Betacoronavirus/pathogenicity , COVID-19 , Chiroptera/microbiology , Codon Usage , Computational Biology , Coronavirus 3C Proteases , Coronavirus Envelope Proteins , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Coronavirus Nucleocapsid Proteins , Cysteine Endopeptidases/metabolism , Eutheria/microbiology , Gene Expression , Humans , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Nucleocapsid Proteins/metabolism , Pandemics , Phosphoproteins , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , RNA-Dependent RNA Polymerase/metabolism , SARS Virus/classification , SARS Virus/pathogenicity , SARS-CoV-2 , Sequence Homology, Nucleic Acid , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/transmission , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus/metabolism , Viral Envelope Proteins/metabolism , Viral Nonstructural Proteins/metabolism
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