RESUMEN
Novel coronavirus (nCoV) namely "SARS-CoV-2" is being found responsible for current PANDEMIC commenced from Wuhan (China) since December 2019 and has been described with epidemiological linkage to China in about 221 countries and territories until now. In this study we have characterized the genetic lineage of SARS-CoV-2 and report the recombination within the genus and subgenus of coronaviruses. Phylogenetic relationship of thirty nine coronaviruses belonging to its four genera and five subgenera was analyzed by using the Neighbor-joining method using MEGA 6.0. Phylogenetic trees of full length genome, various proteins (spike, envelope, membrane and nucleocapsid) nucleotide sequences were constructed separately. Putative recombination was probed via RDP4. Our analysis describes that the "SARS-CoV-2" although shows great similarity to Bat-SARS-CoVs sequences through whole genome (giving sequence similarity 89%), exhibits conflicting grouping with the Bat-SARS-like coronavirus sequences (MG772933 and MG772934). Furthermore, seven recombination events were observed in SARS-CoV-2 (NC_045512) by RDP4. But not a single recombination event fulfills the high level of certainty. Recombination mostly housed in spike protein genes than rest of the genome indicating breakpoint cluster arises beyond the 95% and 99% breakpoint density intervals. Genetic similarity levels observed among "SARS-CoV-2" and Bat-SARS-CoVs advocated that the latter did not exhibit the specific variant that cause outbreak in humans, proposing a suggestion that "SARS-CoV-2" has originated possibly from bats. These genomic features and their probable association with virus characteristics along with virulence in humans require further consideration.(AU)
O novo coronavírus (nCoV), nomeadamente "SARS-CoV-2", foi considerado responsável pela pandemia atual iniciada em Wuhan (China) desde dezembro de 2019 e foi descrito com ligação epidemiológica à China em cerca de 221 países e territórios até agora. Neste estudo, caracterizamos a linhagem genética do SARS-CoV-2 e relatamos a recombinação dentro do gênero e subgênero dos coronavírus. A relação filogenética de 39 coronavírus pertencentes a seus quatro gêneros e cinco subgêneros foi analisada usando o método de Neighbour-joining usando MEGA 6.0. Árvores filogenéticas do genoma de comprimento total, várias proteínas (espícula, envelope, membrana e nucleocapsídeo), sequências de nucleotídeos foram construídas separadamente. A recombinação putativa foi testada via RDP4. Nossa análise descreve que o "SARS-CoV-2", embora mostre grande semelhança com as sequências de Bat-SARS-CoVs em todo o genoma (dando semelhança de sequência de 89%), exibe agrupamento conflitante com as sequências de coronavírus do tipo Bat-SARS (MG772933 e MG772934) Além disso, sete eventos de recombinação foram observados em SARS-CoV-2 (NC045512) por RDP4. Mas nem um único evento de recombinação preenche o alto nível de certeza. A recombinação está alojada mais em genes de proteína de pico, principalmente, do que no resto do genoma, indicando que o cluster de ponto de interrupção surge além dos intervalos de densidade de ponto de interrupção de 95% e 99%. Os níveis de similaridade genética observados entre "SARS-CoV-2" e Bat-SARS-CoVs defendem que o último não exibe a variante específica que causa surto em humanos, sugerindo que "SARS-CoV-2" tenha se originado possivelmente de morcegos. Essas características genômicas e sua provável associação com as características do vírus, juntamente com a virulência em humanos, requerem uma consideração mais aprofundada.(AU)
Asunto(s)
Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , FilogeniaRESUMEN
Novel coronavirus (nCoV) namely "SARS-CoV-2" is being found responsible for current PANDEMIC commenced from Wuhan (China) since December 2019 and has been described with epidemiological linkage to China in about 221 countries and territories until now. In this study we have characterized the genetic lineage of SARS-CoV-2 and report the recombination within the genus and subgenus of coronaviruses. Phylogenetic relationship of thirty nine coronaviruses belonging to its four genera and five subgenera was analyzed by using the Neighbor-joining method using MEGA 6.0. Phylogenetic trees of full length genome, various proteins (spike, envelope, membrane and nucleocapsid) nucleotide sequences were constructed separately. Putative recombination was probed via RDP4. Our analysis describes that the "SARS-CoV-2" although shows great similarity to Bat-SARS-CoVs sequences through whole genome (giving sequence similarity 89%), exhibits conflicting grouping with the Bat-SARS-like coronavirus sequences (MG772933 and MG772934). Furthermore, seven recombination events were observed in SARS-CoV-2 (NC_045512) by RDP4. But not a single recombination event fulfills the high level of certainty. Recombination mostly housed in spike protein genes than rest of the genome indicating breakpoint cluster arises beyond the 95% and 99% breakpoint density intervals. Genetic similarity levels observed among "SARS-CoV-2" and Bat-SARS-CoVs advocated that the latter did not exhibit the specific variant that cause outbreak in humans, proposing a suggestion that "SARS-CoV-2" has originated possibly from bats. These genomic features and their probable association with virus characteristics along with virulence in humans require further consideration.
O novo coronavírus (nCoV), nomeadamente "SARS-CoV-2", foi considerado responsável pela pandemia atual iniciada em Wuhan (China) desde dezembro de 2019 e foi descrito com ligação epidemiológica à China em cerca de 221 países e territórios até agora. Neste estudo, caracterizamos a linhagem genética do SARS-CoV-2 e relatamos a recombinação dentro do gênero e subgênero dos coronavírus. A relação filogenética de 39 coronavírus pertencentes a seus quatro gêneros e cinco subgêneros foi analisada usando o método de Neighbour-joining usando MEGA 6.0. Árvores filogenéticas do genoma de comprimento total, várias proteínas (espícula, envelope, membrana e nucleocapsídeo), sequências de nucleotídeos foram construídas separadamente. A recombinação putativa foi testada via RDP4. Nossa análise descreve que o "SARS-CoV-2", embora mostre grande semelhança com as sequências de Bat-SARS-CoVs em todo o genoma (dando semelhança de sequência de 89%), exibe agrupamento conflitante com as sequências de coronavírus do tipo Bat-SARS (MG772933 e MG772934) Além disso, sete eventos de recombinação foram observados em SARS-CoV-2 (NC045512) por RDP4. Mas nem um único evento de recombinação preenche o alto nível de certeza. A recombinação está alojada mais em genes de proteína de pico, principalmente, do que no resto do genoma, indicando que o cluster de ponto de interrupção surge além dos intervalos de densidade de ponto de interrupção de 95% e 99%. Os níveis de similaridade genética observados entre "SARS-CoV-2" e Bat-SARS-CoVs defendem que o último não exibe a variante específica que causa surto em humanos, sugerindo que "SARS-CoV-2" tenha se originado possivelmente de morcegos. Essas características genômicas e sua provável associação com as características do vírus, juntamente com a virulência em humanos, requerem uma consideração mais aprofundada.
Asunto(s)
Filogenia , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genéticaRESUMEN
RESUMEN Fundamento: La variabilidad clínica de la infección por el SARS-CoV-2 se debe, en parte, a factores genéticos. Objetivo: Describir los principales genes de susceptibilidad a la Covid-19. Metodología: Se realizó una revisión bibliográfica en Google Académico, SciELO, Annual Reviews y PubMed Central. Los descriptores que se utilizaron para la búsqueda de los documentos fueron consultados en el DeCS, estos fueron: SARS-CoV-2, Covid-19, genética y predisposición genética a la enfermedad. Se seleccionaron artículos disponibles a texto completo en inglés y en español, preferentemente de revistas arbitradas por pares. Resultados: Entre los genes implicados en la infección por el SARS-CoV-2 se encuentran DDX1 que promueve la replicación viral, IFITM1, IFITM2, IFITM3, IFNAR2 que codifican proteínas inducidas por el interferón, los genes de receptores (ACE2, ANPEP, DPP4), los genes de proteasas (TMPRSS2, furin, TMPRSS11D, CTSL, CTSB) que contribuyen a la entrada viral, genes de la respuesta inmune como ABO y metalopeptidasas como la familia ADAM. Se han detectado polimorfismos genéticos de riesgo. Conclusiones: En la infección por el SARS-CoV-2 se produce una compleja interrelación entre factores ambientales y genéticos que determinan la susceptibilidad de las personas a la Covid y su gravedad. El papel de los genes en la susceptibilidad a la Covid-19 deberá continuar investigándose.
ABSTRACT Background: The clinical variability of SARS-CoV-2 infection is partially due to genetic factors. Objective: To describe the main Covid-19 susceptibility genes. Methodology: A literature review was performed in Google Scholar, SciELO, Annual Reviews and PubMed Central. The descriptors used to search the documents were consulted in DeCS: SARS-CoV-2, Covid-19, genetics and genetic predisposition to disease. Full text articles available in English and Spanish were selected, rather from peer-reviewed journals. Results: Genes involved in SARS-CoV-2 infection include DDX1 which promotes viral replication, IFITM1, IFITM2, IFITM3, IFNAR2 encoding interferon-induced proteins, receptor genes (ACE2, ANPEP, DPP4), protease genes (TMPRSS2, furin, TMPRSS11D, CTSL, CTSB) that contribute to viral entry, immune response genes such as ABO and metallopeptidases such as the ADAM family. Risk genetic polymorphisms have been detected. Conclusions: In SARS-CoV-2 infection, there is a complex interaction between environmental and genetic factors that determine the susceptibility of individuals to Covid and its severity. The role of genes in Covid-19 susceptibility should be further investigated.
Asunto(s)
Infecciones por Coronavirus/genética , Predisposición Genética a la Enfermedad , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genéticaRESUMEN
Fundamento: La variabilidad clínica de la infección por el SARS-CoV-2 se debe, en parte, a factores genéticos.Objetivo: Describir los principales genes de susceptibilidad a la Covid-19.Metodología: Se realizó una revisión bibliográfica en Google Académico, SciELO, Annual Reviews y PubMedCentral. Los descriptores que se utilizaron para la búsqueda de los documentos fueron consultados en el DeCS,estos fueron: SARS-CoV-2, Covid-19, genética y predisposición genética a la enfermedad. Se seleccionaronartículos disponibles a texto completo en inglés y en español, preferentemente de revistas arbitradas por pares.Resultados: Entre los genes implicados en la infección por el SARS-CoV-2 se encuentran DDX1 que promuevela replicación viral, IFITM1, IFITM2, IFITM3, IFNAR2 que codifican proteínas inducidas por el interferón, losgenes de receptores (ACE2, ANPEP, DPP4), los genes de proteasas (TMPRSS2, furin, TMPRSS11D, CTSL,CTSB) que contribuyen a la entrada viral, genes de la respuesta inmune como ABO y metalopeptidasas comola familia ADAM. Se han detectado polimorfismos genéticos de riesgo.Conclusiones: En la infección por el SARS-CoV-2 se produce una compleja interrelación entre factoresambientales y genéticos que determinan la susceptibilidad de las personas a la Covid y su gravedad. El papelde los genes en la susceptibilidad a la Covid-19 deberá continuar investigándose [AU]
Asunto(s)
Humanos , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Infecciones por Coronavirus/genética , Predisposición Genética a la EnfermedadRESUMEN
Spike (S) glycoproteins mediate the coronavirus entry into the host cell. The S1 subunit of S-proteins contains the receptor-binding domain (RBD) that is able to recognize different host receptors, highlighting its remarkable capacity to adapt to their hosts along the viral evolution. While RBD in spike proteins is determinant for the virus-receptor interaction, the active residues lie at the receptor-binding motif (RBM), a region located in RBD that plays a fundamental role binding the outer surface of their receptors. Here, we address the hypothesis that SARS-CoV and SARS-CoV-2 strains able to use angiotensin-converting enzyme 2 (ACE2) proteins have adapted their RBM along the viral evolution to explore specific conformational topology driven by the residues YGF to infect host cells. We also speculate that this YGF-based mechanism can act as a protein signature located at the RBM to distinguish coronaviruses able to use ACE2 as a cell entry receptor.Communicated by Ramaswamy H. Sarma.
Asunto(s)
COVID-19 , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Humanos , SARS-CoV-2/metabolismo , Enzima Convertidora de Angiotensina 2/metabolismo , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Aminoácidos/metabolismo , Unión Proteica , Glicoproteína de la Espiga del Coronavirus/químicaRESUMEN
COVID-19 is an infection caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), which has caused a global outbreak. Current research efforts are focused on the understanding of the molecular mechanisms involved in SARS-CoV-2 infection in order to propose drug-based therapeutic options. Transcriptional changes due to epigenetic regulation are key host cell responses to viral infection and have been studied in SARS-CoV and MERS-CoV; however, such changes are not fully described for SARS-CoV-2. In this study, we analyzed multiple transcriptomes obtained from cell lines infected with MERS-CoV, SARS-CoV, and SARS-CoV-2, and from COVID-19 patient-derived samples. Using integrative analyses of gene co-expression networks and de-novo pathway enrichment, we characterize different gene modules and protein pathways enriched with Transcription Factors or Epifactors relevant for SARS-CoV-2 infection. We identified EP300, MOV10, RELA, and TRIM25 as top candidates, and more than 60 additional proteins involved in the epigenetic response during viral infection that has therapeutic potential. Our results show that targeting the epigenetic machinery could be a feasible alternative to treat COVID-19.
Asunto(s)
COVID-19/genética , Epigénesis Genética/genética , SARS-CoV-2/genética , Transcriptoma/genética , COVID-19/virología , Perfilación de la Expresión Génica , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Coronavirus del Síndrome Respiratorio de Oriente Medio/patogenicidad , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/patogenicidad , SARS-CoV-2/patogenicidad , Transducción de Señal/genéticaRESUMEN
In December 2019, rising pneumonia cases caused by a novel ß-coronavirus (SARS-CoV-2) occurred in Wuhan, China, which has rapidly spread worldwide, causing thousands of deaths. The WHO declared the SARS-CoV-2 outbreak as a public health emergency of international concern, since then several scientists are dedicated to its study. It has been observed that many human viruses have codon usage biases that match highly expressed proteins in the tissues they infect and depend on the host cell machinery for the replication and co-evolution. In this work, we analysed 91 molecular features and codon usage patterns for 339 viral genes and 463 human genes that consisted of 677,873 codon positions. Hereby, we selected the highly expressed genes from human lung tissue to perform computational studies that permit to compare their molecular features with those of SARS, SARS-CoV-2 and MERS genes. The integrated analysis of all the features revealed that certain viral genes and overexpressed human genes have similar codon usage patterns. The main pattern was the A/T bias that together with other features could propitiate the viral infection, enhanced by a host dependant specialization of the translation machinery of only some of the overexpressed genes. The envelope protein E, the membrane glycoprotein M and ORF7 could be further benefited. This could be the key for a facilitated translation and viral replication conducting to different comorbidities depending on the genetic variability of population due to the host translation machinery. This is the first codon usage approach that reveals which human genes could be potentially deregulated due to the codon usage similarities between the host and the viral genes when the virus is already inside the human cells of the lung tissues. Our work leaded to the identification of additional highly expressed human genes which are not the usual suspects but might play a role in the viral infection and settle the basis for further research in the field of human genetics associated with new viral infections. To identify the genes that could be deregulated under a viral infection is important to predict the collateral effects and determine which individuals would be more susceptible based on their genetic features and comorbidities associated.
Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/virología , Codón/genética , Uso de Codones , Biología Computacional/métodos , Coronavirus/genética , Infecciones por Coronavirus/metabolismo , Genes Virales , Genoma Viral , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Filogenia , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , SARS-CoV-2/genéticaRESUMEN
In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of coronaviruses in the aftermath of the 2002-2003 severe acute respiratory syndrome (SARS) and 2012 Middle East respiratory syndrome (MERS) outbreaks. Furthermore, genome sequencing and bioinformatic analysis have had an unprecedented relevance in the battle against the 2019-2020 coronavirus disease 2019 (COVID-19) pandemic, the newest and most devastating outbreak caused by a coronavirus in the history of mankind. Here, we review how genomic information has been used to tackle outbreaks caused by emerging, highly pathogenic, betacoronavirus strains, emphasizing on SARS-CoV, MERS-CoV and SARS-CoV-2. We focus on shared genomic features of the betacoronaviruses and the application of genomic information to phylogenetic analysis, molecular epidemiology and the design of diagnostic systems, potential drugs and vaccine candidates.
Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/virología , Genoma Viral , Pandemias/prevención & control , Neumonía Viral/virología , Animales , Betacoronavirus/inmunología , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Diseño de Fármacos , Genes Virales , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Epidemiología Molecular , Filogenia , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , SARS-CoV-2 , Síndrome Respiratorio Agudo Grave/virología , Vacunas Virales/genética , Vacunas Virales/inmunologíaRESUMEN
El objetivo de este artículo es proporcionar una guía que sirva para la interpretación y seguimiento de los esfuerzos que se están desarrollando en todo el mundo con el objetivo de obtener una vacuna que pueda generar inmunidad contra el nuevo coronavirus SARS-CoV-2 de 2019, el agente causante de la enfermedad por coronavirus denominada COVID-19. Cinco meses después de haber sido detectada la enfermedad, ya hay 102 vacunas en distintos estadios de desarrollo, registradas por la Organización Mundial de la Salud (OMS), correspondientes a 8 plataformas vacunales con diferentes estrategias, y todos los días aparecen nuevas. Esto representará un enorme desafío de organismos internacionales, para la evaluación, comparación y selección de aquellas que cumplan con los criterios regulatorios indispensables de seguridad y eficacia y que, por otro lado, puedan ser producidas en cantidades suficientes para abastecer la demanda mundial. (AU)
The objective of this article is to provide a guide to help the interpretation and monitoring the efforts that are being carried out worldwide to obtain a vaccine that will be able to generate immunity against the new 2019 SARS-CoV-2 coronavirus, the viral agent causes the disease named COVID-19. Five months after the disease was detected, there are already 102 vaccines at different stages of development, registered by World Health Organization (WHO), corresponding to 8 vaccination platforms base on different strategies, and every day new ones appear. This will represent a huge challenge for international organizations, to evaluate, compare and selects those that will meet the essential regulatory criteria of safety and efficacy and that, would be able to be produced in enough quantities to supply the worldwide demand. Key words: SARS-Cov-2 vaccine, vaccine platform, COVID-19 strategy, attenuated virus, viral vector, viral proteins, viral DNA, viral RNA, nucleic acids, viral like particles, WHO. (AU)
Asunto(s)
Humanos , Masculino , Femenino , Infecciones por Coronavirus/terapia , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunología , Neumonía Viral/terapia , ADN/uso terapéutico , ARN/uso terapéutico , Vacunas/uso terapéutico , Ácidos Nucleicos/uso terapéutico , Proteína S/inmunología , Infecciones por Coronavirus/virología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/fisiología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Vectores de EnfermedadesRESUMEN
At the beginning of the 21st century, a new deadly infectious disease known as severe acute respiratory syndrome (SARS) was recognized as a global public health threat. Subsequently, ten years after the initial SARS cases occurred in 2002, new cases of another atypical respiratory disease caused worldwide concern. This disease became known as Middle East respiratory syndrome (MERS) and was even more lethal than SARS. Currently, history has repeated itself with the emergence of a new Chinese epidemic at the end of 2019. For this respiratory disease, called COVID-19, a novel coronavirus (SARS-CoV-2) was identified as the etiologic agent. In sum, SARS, MERS and COVID-19 are caused by recently discovered coronaviruses that cause flu-like illnesses, but with a clinical outcome that tends to be more severe. As a result of the current importance of coronaviruses in global public health, we conducted a review to summarize and update, above all, the epidemiological historical aspects of the three major diseases in humans caused by coronaviral infection.
Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/virología , Coronavirus del Síndrome Respiratorio de Oriente Medio/fisiología , Neumonía Viral/virología , Síndrome Respiratorio Agudo Grave/virología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/fisiología , Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , COVID-19 , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Pandemias , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/aislamiento & purificación , SARS-CoV-2RESUMEN
I have been researching coronaviruses for more than forty years. This viewpoint summarizes some of the major findings in coronavirus research made before the SARS epidemic and how they inform current research on the newly emerged SARS-CoV-2.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus , Coronavirus , ARN Viral , Proteínas Virales , Betacoronavirus/genética , Betacoronavirus/patogenicidad , COVID-19 , Coronavirus/genética , Coronavirus/patogenicidad , Coronavirus/fisiología , Infecciones por Coronavirus/epidemiología , Genoma , Humanos , Evasión Inmune , Relaciones Interprofesionales , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Coronavirus del Síndrome Respiratorio de Oriente Medio/patogenicidad , Pandemias , Filogenia , Neumonía Viral/epidemiología , ARN Viral/genética , Investigación/tendencias , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/patogenicidad , SARS-CoV-2 , Proteínas Virales/fisiología , Virión , Virología/tendenciasRESUMEN
The city of Wuhan, Hubei province, China, was the origin of a severe pneumonia outbreak in December 2019, attributed to a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), causing a total of 2761 deaths and 81109 cases (25 February 2020). SARS-CoV-2 belongs to genus Betacoronavirus, subgenus Sarbecovirus. The polyprotein 1ab (pp1ab) remains unstudied thoroughly since it is similar to other sarbecoviruses. In this short communication, we performed phylogenetic-structural sequence analysis of pp1ab protein of SARS-CoV-2. The analysis showed that the viral pp1ab has not changed in most isolates throughout the outbreak time, but interestingly a deletion of 8 aa in the virulence factor nonstructural protein 1 was found in a virus isolated from a Japanese patient that did not display critical symptoms. While comparing pp1ab protein with other betacoronaviruses, we found a 42 amino acid signature that is only present in SARS-CoV-2 (AS-SCoV2). Members from clade 2 of sarbecoviruses have traces of this signature. The AS-SCoV2 located in the acidic-domain of papain-like protein of SARS-CoV-2 and bat-SL-CoV-RatG13 guided us to suggest that the novel 2019 coronavirus probably emerged by genetic drift from bat-SL-CoV-RaTG13. The implication of this amino acid signature in papain-like protein structure arrangement and function is something worth to be explored.