RESUMEN
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) not only caused the COVID-19 pandemic but also had a major impact on farmed mink production in several European countries. In Denmark, the entire population of farmed mink (over 15 million animals) was culled in late 2020. During the period of June to November 2020, mink on 290 farms (out of about 1100 in the country) were shown to be infected with SARS-CoV-2. Genome sequencing identified changes in the virus within the mink and it is estimated that about 4000 people in Denmark became infected with these mink virus variants. However, the routes of transmission of the virus to, and from, the mink have been unclear. Phylogenetic analysis revealed the generation of multiple clusters of the virus within the mink. Detailed analysis of changes in the virus during replication in mink and, in parallel, in the human population in Denmark, during the same time period, has been performed here. The majority of cases in mink involved variants with the Y453F substitution and the H69/V70 deletion within the Spike (S) protein; these changes emerged early in the outbreak. However, further introductions of the virus, by variants lacking these changes, from the human population into mink also occurred. Based on phylogenetic analysis of viral genome data, we estimate, using a conservative approach, that about 17 separate examples of mink to human transmission occurred in Denmark but up to 59 such events (90% credible interval: (39-77)) were identified using parsimony to count cross-species jumps on transmission trees inferred using Bayesian methods. Using the latter approach, 136 jumps (90% credible interval: (117-164)) from humans to mink were found, which may underlie the farm-to-farm spread. Thus, transmission of SARS-CoV-2 from humans to mink, mink to mink, from mink to humans and between humans were all observed.
Asunto(s)
COVID-19 , Visón , Filogenia , SARS-CoV-2 , Visón/virología , COVID-19/transmisión , COVID-19/virología , COVID-19/epidemiología , COVID-19/veterinaria , SARS-CoV-2/genética , Animales , Dinamarca/epidemiología , Humanos , Pandemias , Granjas , Betacoronavirus/genética , Betacoronavirus/clasificación , Genoma Viral , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/transmisión , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense, single-stranded RNA genome-containing virus which has infected millions of people all over the world. The virus has been mutating rapidly enough, resulting in the emergence of new variants and sub-variants which have reportedly been spread from Wuhan city in China, the epicenter of the virus, to the rest of China and all over the world. The occurrence of mutations in the viral genome, especially in the viral spike protein region, has resulted in the evolution of multiple variants and sub-variants which gives the virus the benefit of host immune evasion and thus renders modern-day vaccines and therapeutics ineffective. Therefore, there is a continuous need to study the genetic characteristics and evolutionary dynamics of the SARS-CoV-2 variants. Hence, in this study, a total of 832 complete genomes of SARS-CoV-2 variants from the cities of Taiyuan and Wuhan in China was genetically characterized and their phylogenetic and evolutionary dynamics studied using phylogenetics, genetic similarity, and phylogenetic network analyses. This study shows that the four most prevalent lineages in Taiyuan and Wuhan are as follows: the Omicron lineages EG.5.1.1, followed by HK.3, FY.3, and XBB.1.16 (Pangolin classification), and clades 23F (EG.5.1), followed by 23H (HK.3), 22F (XBB), and 23D (XBB.1.9) (Nextclade classification), and lineage B followed by the Omicron FY.3, lineage A, and Omicron FL.2.3 (Pangolin classification), and the clades 19A, followed by 22F (XBB), 23F (EG.5.1), and 23H (HK.3) (Nextclade classification), respectively. Furthermore, our genetic similarity analysis show that the SARS-CoV-2 clade 19A-B.4 from Wuhan (name starting with 412981) has the least genetic similarity of about 95.5% in the spike region of the genome as compared to the query sequence of Omicron XBB.2.3.2 from Taiyuan (name starting with 18495234), followed by the Omicron FR.1.4 from Taiyuan (name starting with 18495199) with ~97.2% similarity and Omicron DY.3 (name starting with 17485740) with ~97.9% similarity. The rest of the variants showed ≥98% similarity with the query sequence of Omicron XBB.2.3.2 from Taiyuan (name starting with 18495234). In addition, our recombination analysis results show that the SARS-CoV-2 variants have three statistically significant recombinant events which could have possibly resulted in the emergence of Omicron XBB.1.16 (recombination event 3), FY.3 (recombination event 5), and FL.2.4 (recombination event 7), suggesting some very important information regarding viral evolution. Also, our phylogenetic tree and network analyses show that there are a total of 14 clusters and more than 10,000 mutations which may have probably resulted in the emergence of cluster-I, followed by 47 mutations resulting in the emergence of cluster-II and so on. The clustering of the viral variants of both cities reveals significant information regarding the phylodynamics of the virus among them. The results of our temporal phylogenetic analysis suggest that the variants of Taiyuan have likely emerged as independent variants separate from the variants of Wuhan. This study, to the best of our knowledge, is the first ever genetic comparative study between Taiyuan and Wuhan cities in China. This study will help us better understand the virus and cope with the emergence and spread of new variants at a local as well as an international level, and keep the public health authorities informed for them to make better decisions in designing new viral vaccines and therapeutics. It will also help the outbreak investigators to better examine any future outbreak.
Asunto(s)
COVID-19 , Evolución Molecular , Genoma Viral , Mutación , Filogenia , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/clasificación , China/epidemiología , Humanos , COVID-19/virología , COVID-19/epidemiología , Glicoproteína de la Espiga del Coronavirus/genética , Ciudades , Betacoronavirus/genética , Betacoronavirus/clasificaciónRESUMEN
SARS-CoV-2, the seventh coronavirus known to infect humans, can cause severe life-threatening respiratory pathologies. To better understand SARS-CoV-2 evolution, genome-wide analyses have been made, including the general characterization of its codons usage profile. Here we present a bioinformatic analysis of the evolution of SARS-CoV-2 codon usage over time using complete genomes collected since December 2019. Our results show that SARS-CoV-2 codon usage pattern is antagonistic to, and it is getting farther away from that of the human host. Further, a selection of deoptimized codons over time, which was accompanied by a decrease in both the codon adaptation index and the effective number of codons, was observed. All together, these findings suggest that SARS-CoV-2 could be evolving, at least from the perspective of the synonymous codon usage, to become less pathogenic.
Asunto(s)
COVID-19/epidemiología , COVID-19/virología , Uso de Codones , Codón , Evolución Molecular , Pandemias , SARS-CoV-2/genética , Betacoronavirus/clasificación , Betacoronavirus/genética , Regulación Viral de la Expresión Génica , Genoma Viral , Genómica/métodos , Humanos , Sistemas de Lectura Abierta , Especificidad de Órganos , FilogeniaRESUMEN
Recent studies suggest that coronaviruses circulate widely in Southeast Asian bat species and that the progenitors of the SARS-Cov-2 virus could have originated in rhinolophid bats in the region. Our objective was to assess the diversity and circulation patterns of coronavirus in several bat species in Southeast Asia. We undertook monthly live-capture sessions and sampling in Cambodia over 17 months to cover all phases of the annual reproduction cycle of bats and test specifically the association between their age and CoV infection status. We additionally examined current information on the reproductive phenology of Rhinolophus and other bat species presently known to occur in mainland southeast China, Vietnam, Laos and Cambodia. Results from our longitudinal monitoring (573 bats belonging to 8 species) showed an overall proportion of positive PCR tests for CoV of 4.2% (24/573) in cave-dwelling bats from Kampot and 4.75% (22/463) in flying-foxes from Kandal. Phylogenetic analysis showed that the PCR amplicon sequences of CoVs (n = 46) obtained clustered in Alphacoronavirus and Betacoronavirus. Interestingly, Hipposideros larvatus sensu lato harbored viruses from both genera. Our results suggest an association between positive detections of coronaviruses and juvenile and immature bats in Cambodia (OR = 3.24 [1.46-7.76], p = 0.005). Since the limited data presently available from literature review indicates that reproduction is largely synchronized among rhinolophid and hipposiderid bats in our study region, particularly in its more seasonal portions (above 16° N), this may lead to seasonal patterns in CoV circulation. Overall, our study suggests that surveillance of CoV in insectivorous bat species in Southeast Asia, including SARS-CoV-related coronaviruses in rhinolophid bats, could be targeted from June to October for species exhibiting high proportions of juveniles and immatures during these months. It also highlights the need to develop long-term longitudinal surveys of bats and improve our understanding of their ecology in the region, for both biodiversity conservation and public health reasons.
Asunto(s)
Alphacoronavirus/genética , Betacoronavirus/genética , COVID-19/transmisión , Quirópteros/crecimiento & desarrollo , SARS-CoV-2/genética , Alphacoronavirus/clasificación , Animales , Asia Sudoriental/epidemiología , Betacoronavirus/clasificación , COVID-19/epidemiología , COVID-19/virología , Cambodia/epidemiología , Quirópteros/clasificación , Quirópteros/virología , Epidemias/prevención & control , Evolución Molecular , Genoma Viral/genética , Geografía , Humanos , Estudios Longitudinales , Masculino , Filogenia , SARS-CoV-2/clasificación , SARS-CoV-2/fisiología , Especificidad de la EspecieRESUMEN
According to various estimates, only a small percentage of existing viruses have been discovered, naturally much less being represented in the genomic databases. High-throughput sequencing technologies develop rapidly, empowering large-scale screening of various biological samples for the presence of pathogen-associated nucleotide sequences, but many organisms are yet to be attributed specific loci for identification. This problem particularly impedes viral screening, due to vast heterogeneity in viral genomes. In this paper, we present a new bioinformatic pipeline, VirIdAl, for detecting and identifying viral pathogens in sequencing data. We also demonstrate the utility of the new software by applying it to viral screening of the feces of bats collected in the Moscow region, which revealed a significant variety of viruses associated with bats, insects, plants, and protozoa. The presence of alpha and beta coronavirus reads, including the MERS-like bat virus, deserves a special mention, as it once again indicates that bats are indeed reservoirs for many viral pathogens. In addition, it was shown that alignment-based methods were unable to identify the taxon for a large proportion of reads, and we additionally applied other approaches, showing that they can further reveal the presence of viral agents in sequencing data. However, the incompleteness of viral databases remains a significant problem in the studies of viral diversity, and therefore necessitates the use of combined approaches, including those based on machine learning methods.
Asunto(s)
Alphacoronavirus/aislamiento & purificación , Betacoronavirus/aislamiento & purificación , Quirópteros/virología , Genoma Viral/genética , Metagenoma/genética , Alphacoronavirus/clasificación , Alphacoronavirus/genética , Animales , Betacoronavirus/clasificación , Betacoronavirus/genética , Quirópteros/genética , Biología Computacional/métodos , Heces/virología , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica/métodos , Moscú , Phycodnaviridae/clasificación , Phycodnaviridae/genética , Phycodnaviridae/aislamiento & purificación , Análisis de Secuencia de ADNAsunto(s)
Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , COVID-19/virología , Quirópteros/virología , Evolución Molecular , Filogenia , SARS-CoV-2/genética , Zoonosis Virales/virología , Animales , Betacoronavirus/clasificación , COVID-19/transmisión , Línea Celular , China , Furina/metabolismo , Genoma Viral , Humanos , Laos , Modelos Animales , Preimpresos como Asunto , SARS-CoV-2/clasificación , SARS-CoV-2/aislamiento & purificación , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Zoonosis Virales/transmisiónAsunto(s)
COVID-19/transmisión , COVID-19/virología , SARS-CoV-2 , Zoonosis Virales , Animales , Animales Domésticos/virología , Animales Salvajes/virología , Betacoronavirus/clasificación , Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , China , Quirópteros/virología , Reservorios de Enfermedades/virología , Evolución Molecular , Humanos , Carne , SARS-CoV-2/clasificación , SARS-CoV-2/genética , SARS-CoV-2/fisiología , Zoonosis Virales/virologíaRESUMEN
The source of the COVID-19 pandemic is unknown, but the natural host of the progenitor sarbecovirus is thought to be Asian horseshoe (rhinolophid) bats. We identified and sequenced a novel sarbecovirus (RhGB01) from a British horseshoe bat, at the western extreme of the rhinolophid range. Our results extend both the geographic and species ranges of sarbecoviruses and suggest their presence throughout the horseshoe bat distribution. Within the spike protein receptor binding domain, but excluding the receptor binding motif, RhGB01 has a 77% (SARS-CoV-2) and 81% (SARS-CoV) amino acid homology. While apparently lacking hACE2 binding ability, and hence unlikely to be zoonotic without mutation, RhGB01 presents opportunity for SARS-CoV-2 and other sarbecovirus homologous recombination. Our findings highlight that the natural distribution of sarbecoviruses and opportunities for recombination through intermediate host co-infection are underestimated. Preventing transmission of SARS-CoV-2 to bats is critical with the current global mass vaccination campaign against this virus.
Asunto(s)
Betacoronavirus/clasificación , Betacoronavirus/aislamiento & purificación , Quirópteros/virología , Secuencia de Aminoácidos , Animales , Europa (Continente) , Genoma Viral , Metagenómica , Filogenia , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/químicaRESUMEN
Despite its clinical importance, the SARS-CoV-2 gene set remains unresolved, hindering dissection of COVID-19 biology. We use comparative genomics to provide a high-confidence protein-coding gene set, characterize evolutionary constraint, and prioritize functional mutations. We select 44 Sarbecovirus genomes at ideally-suited evolutionary distances, and quantify protein-coding evolutionary signatures and overlapping constraint. We find strong protein-coding signatures for ORFs 3a, 6, 7a, 7b, 8, 9b, and a novel alternate-frame gene, ORF3c, whereas ORFs 2b, 3d/3d-2, 3b, 9c, and 10 lack protein-coding signatures or convincing experimental evidence of protein-coding function. Furthermore, we show no other conserved protein-coding genes remain to be discovered. Mutation analysis suggests ORF8 contributes to within-individual fitness but not person-to-person transmission. Cross-strain and within-strain evolutionary pressures agree, except for fewer-than-expected within-strain mutations in nsp3 and S1, and more-than-expected in nucleocapsid, which shows a cluster of mutations in a predicted B-cell epitope, suggesting immune-avoidance selection. Evolutionary histories of residues disrupted by spike-protein substitutions D614G, N501Y, E484K, and K417N/T provide clues about their biology, and we catalog likely-functional co-inherited mutations. Previously reported RNA-modification sites show no enrichment for conservation. Here we report a high-confidence gene set and evolutionary-history annotations providing valuable resources and insights on SARS-CoV-2 biology, mutations, and evolution.
Asunto(s)
COVID-19/virología , Genoma Viral/genética , Mutación , SARS-CoV-2/genética , Betacoronavirus/clasificación , Betacoronavirus/genética , Codón , Evolución Molecular , Genes Virales , Aptitud Genética , Variación Genética , Sistemas de Lectura Abierta , Filogenia , Glicoproteína de la Espiga del Coronavirus/genética , Proteínas Virales/genéticaRESUMEN
BACKGROUND: Mathematical approaches have been for decades used to probe the structure of DNA sequences. This has led to the development of Bioinformatics. In this exploratory work, a novel mathematical method is applied to probe the DNA structure of two related viral families: those of coronaviruses and those of influenza viruses. The coronaviruses are SARS-CoV-2, SARS-CoV-1, and MERS. The influenza viruses include H1N1-1918, H1N1-2009, H2N2-1957, and H3N2-1968. METHODS: The mathematical method used is the slow feature analysis (SFA), a rather new but promising method to delineate complex structure in DNA sequences. RESULTS: The analysis indicates that the DNA sequences exhibit an elaborate and convoluted structure akin to complex networks. We define a measure of complexity and show that each DNA sequence exhibits a certain degree of complexity within itself, while at the same time there exists complex inter-relationships between the sequences within a family and between the two families. From these relationships, we find evidence, especially for the coronavirus family, that increasing complexity in a sequence is associated with higher transmission rate but with lower mortality. CONCLUSIONS: The complexity measure defined here may hold a promise and could become a useful tool in the prediction of transmission and mortality rates in future new viral strains.
Asunto(s)
Betacoronavirus/clasificación , Betacoronavirus/genética , Virus de la Influenza A/clasificación , Virus de la Influenza A/genética , Modelos Genéticos , Betacoronavirus/fisiología , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Evolución Molecular , Humanos , Virus de la Influenza A/fisiología , Gripe Humana/mortalidad , Gripe Humana/transmisión , Gripe Humana/virología , Análisis de Secuencia de ADN , Especificidad de la Especie , Factores de TiempoRESUMEN
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 227â¯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.
Asunto(s)
Betacoronavirus/clasificación , Aprendizaje Profundo , COVID-19/epidemiología , COVID-19/mortalidad , COVID-19/virología , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/clasificación , Neumonía Viral/epidemiología , Neumonía Viral/mortalidad , Neumonía Viral/virología , SARS-CoV-2/clasificaciónRESUMEN
The coronavirus spike glycoprotein, located on the virion surface, is the key mediator of cell entry and the focus for development of protective antibodies and vaccines. Structural studies show exposed sites on the spike trimer that might be targeted by antibodies with cross-species specificity. Here we isolated two human monoclonal antibodies from immunized humanized mice that display a remarkable cross-reactivity against distinct spike proteins of betacoronaviruses including SARS-CoV, SARS-CoV-2, MERS-CoV and the endemic human coronavirus HCoV-OC43. Both cross-reactive antibodies target the stem helix in the spike S2 fusion subunit which, in the prefusion conformation of trimeric spike, forms a surface exposed membrane-proximal helical bundle. Both antibodies block MERS-CoV infection in cells and provide protection to mice from lethal MERS-CoV challenge in prophylactic and/or therapeutic models. Our work highlights an immunogenic and vulnerable site on the betacoronavirus spike protein enabling elicitation of antibodies with unusual binding breadth.
Asunto(s)
Anticuerpos Monoclonales Humanizados/inmunología , Betacoronavirus/inmunología , Epítopos/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Animales , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/inmunología , Betacoronavirus/clasificación , Camelus , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/virología , Reacciones Cruzadas , Epítopos/química , Epítopos/genética , Humanos , Ratones , Conformación Proteica , Subunidades de Proteína , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has put the global public health at its highest threat around the world. Previous epidemic caused by the acute respiratory syndrome coronavirus (SARS-CoV) in 2002 is also considered since both the coronaviruses resulted in the similar clinical complications. The outbreak caused by the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 had a low rate of disease transmission and death cases. Modes of entry by MERS and SARS coronaviruses are similar to that of SARS-CoV-2, except MERS-CoV utilize different receptor. They all belong to the lineage C of ß-coronavirus. Based on the information from the previous reports, the present review is mainly focused on the mechanisms of disease progression by each of these viruses in association to their strategies to escape the host immunity. The viral entry is the first step of pathogenesis associated with attachment of viral spike protein with host receptor help releasing the viral RNA into the host cell. Models of molecular pathogenesis are outlined with virus strategies escaping the host immunity along with the role of various inflammatory cytokines and chemokines in the process. The molecular aspects of pathogenesis have also been discussed.
Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Evasión Inmune , Betacoronavirus/clasificación , Betacoronavirus/fisiología , Infecciones por Coronavirus/epidemiología , Citocinas/inmunología , Progresión de la Enfermedad , Humanos , Inmunidad Innata , Especificidad de la Especie , Internalización del VirusRESUMEN
The Coronaviridae family includes the seven known human coronaviruses (CoV) that cause mild to moderate respiratory infections (HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1) as well as severe illness and death (MERS-CoV, SARS-CoV, SARS-CoV-2). Severe infections induce hyperinflammatory responses that are often intensified by host adaptive immune pathways to profoundly advance disease severity. Proinflammatory responses are triggered by CoV entry mediated by host cell surface receptors. Interestingly, five of the seven strains use three cell surface metallopeptidases (CD13, CD26, and ACE2) as receptors, whereas the others employ O-acetylated-sialic acid (a key feature of metallopeptidases) for entry. Why CoV evolved to use peptidases as their receptors is unknown, but the peptidase activities of the receptors are dispensable, suggesting the virus uses/benefits from other functions of these molecules. Indeed, these receptors participate in the immune modulatory pathways that contribute to the pathological hyperinflammatory response. This review will focus on the role of CoV receptors in modulating immune responses.
Asunto(s)
Betacoronavirus/clasificación , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Inmunomodulación , Metaloproteasas/inmunología , Receptores de Superficie Celular/inmunología , Receptores de Coronavirus/inmunología , Enzima Convertidora de Angiotensina 2/metabolismo , Animales , Betacoronavirus/metabolismo , Infecciones por Coronavirus/virología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/virología , Humanos , Inmunidad , Interleucina-6/inmunología , Internalización del VirusRESUMEN
COVID-19 is a novel coronavirus with an outbreak of unusual viral pneumonia in Wuhan, China, and then pandemic. Based on its phylogenetic relationships and genomic structures the COVID-19 belongs to genera Betacoronavirus. Human Betacoronaviruses (SARS-CoV-2, SARS-CoV, and MERS-CoV) have many similarities, but also have differences in their genomic and phenotypic structure that can influence their pathogenesis. COVID-19 is containing single-stranded (positive-sense) RNA associated with a nucleoprotein within a capsid comprised of matrix protein. A typical CoV contains at least six ORFs in its genome. All the structural and accessory proteins are translated from the sgRNAs of CoVs. Four main structural proteins are encoded by ORFs 10, 11 on the one-third of the genome near the 3'-terminus. The genetic and phenotypic structure of COVID-19 in pathogenesis is important. This article highlights the most important of these features compared to other Betacoronaviruses.
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COVID-19/virología , SARS-CoV-2/genética , Betacoronavirus/clasificación , Betacoronavirus/genética , Betacoronavirus/patogenicidad , COVID-19/etiología , Genoma Viral , Genotipo , Humanos , Pandemias , Fenotipo , Filogenia , SARS-CoV-2/patogenicidad , SARS-CoV-2/fisiología , Virulencia/genética , Replicación ViralRESUMEN
RNAcentral is a comprehensive database of non-coding RNA (ncRNA) sequences that provides a single access point to 44 RNA resources and >18 million ncRNA sequences from a wide range of organisms and RNA types. RNAcentral now also includes secondary (2D) structure information for >13 million sequences, making RNAcentral the world's largest RNA 2D structure database. The 2D diagrams are displayed using R2DT, a new 2D structure visualization method that uses consistent, reproducible and recognizable layouts for related RNAs. The sequence similarity search has been updated with a faster interface featuring facets for filtering search results by RNA type, organism, source database or any keyword. This sequence search tool is available as a reusable web component, and has been integrated into several RNAcentral member databases, including Rfam, miRBase and snoDB. To allow for a more fine-grained assignment of RNA types and subtypes, all RNAcentral sequences have been annotated with Sequence Ontology terms. The RNAcentral database continues to grow and provide a central data resource for the RNA community. RNAcentral is freely available at https://rnacentral.org.
Asunto(s)
Bases de Datos de Ácidos Nucleicos/organización & administración , Anotación de Secuencia Molecular , ARN no Traducido/genética , Programas Informáticos , Animales , Apicomplexa/clasificación , Apicomplexa/genética , Secuencia de Bases , Betacoronavirus/clasificación , Betacoronavirus/genética , Bases de Datos de Ácidos Nucleicos/provisión & distribución , Hongos/clasificación , Hongos/genética , Ontología de Genes , Humanos , Internet , Conformación de Ácido Nucleico , ARN no Traducido/clasificación , ARN no Traducido/metabolismo , Análisis de Secuencia de ARNRESUMEN
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.
Asunto(s)
Betacoronavirus/clasificación , Betacoronavirus/genética , Recombinación Genética/genética , Glicoproteína de la Espiga del Coronavirus/genética , Intercambio Genético/genética , Genes Virales/genética , Genoma Viral/genética , Especificidad del Huésped/genética , Modelos Genéticos , Polimorfismo Genético , SARS-CoV-2/clasificación , SARS-CoV-2/genética , Tropismo Viral/genéticaRESUMEN
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.
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Betacoronavirus/genética , Variación Genética , Genoma Viral , Betacoronavirus/clasificación , Betacoronavirus/aislamiento & purificación , COVID-19 , China , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Evolución Molecular , Humanos , Pandemias , Filogenia , Neumonía Viral/patología , Neumonía Viral/virología , Poliproteínas , Estructura Terciaria de Proteína , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Proteínas Virales/química , Proteínas Virales/genéticaRESUMEN
The Betacoronavirus genus of mammal-infecting viruses includes three subgenera (Sarbecovirus, Embecovirus, and Merbecovirus), in which most known human coronaviruses, including SARS-CoV-2, cluster. Coronaviruses are prone to host shifts, with recombination and positive selection possibly contributing to their high zoonotic potential. We analyzed the role of these two forces in the evolution of viruses belonging to the Betacoronavirus genus. The results showed that recombination has been pervasive during sarbecovirus evolution, and it is more widespread in this subgenus compared to the other two. In both sarbecoviruses and merbecoviruses, recombination hotspots are clearly observed. Conversely, positive selection was a less prominent force in sarbecoviruses compared to embecoviruses and merbecoviruses and targeted distinct genomic regions in the three subgenera, with S being the major target in sarbecoviruses alone. Overall, the results herein indicate that Betacoronavirus subgenera evolved along different trajectories, which might recapitulate their host preferences or reflect the origins of the presently available coronavirus sequences.
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Betacoronavirus/clasificación , Betacoronavirus/genética , Evolución Molecular , Variación Genética , Recombinación Genética , Selección Genética , Animales , Infecciones por Coronavirus/virología , Genoma Viral , Genómica , Interacciones Microbiota-Huesped , Humanos , Filogenia , Zoonosis ViralesRESUMEN
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-ï¡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.
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-ï¡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.