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1.
Front Cell Infect Microbiol ; 11: 609160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732659

RESUMO

There is an increased global outbreak of diseases caused by coronaviruses affecting respiratory tracts of birds and mammals. Recent dangerous coronaviruses are MERS-CoV, SARS-CoV, and SARS-CoV-2, causing respiratory illness and even failure of several organs. However, profound impact of coronavirus on host cells remains elusive. In this study, we analyzed transcriptome of MERS-CoV, SARS-CoV, and SARS-CoV-2 infected human lung-derived cells, and observed that infection of these coronaviruses all induced increase of retrotransposon expression with upregulation of TET genes. Upregulation of retrotransposon was also observed in SARS-CoV-2 infected human intestinal organoids. Retrotransposon upregulation may lead to increased genome instability and enhanced expression of genes with readthrough from retrotransposons. Therefore, people with higher basal level of retrotransposon such as cancer patients and aged people may have increased risk of symptomatic infection. Additionally, we show evidence supporting long-term epigenetic inheritance of retrotransposon upregulation. We also observed chimeric transcripts of retrotransposon and SARS-CoV-2 RNA for potential human genome invasion of viral fragments, with the front and the rear part of SARS-CoV-2 genome being easier to form chimeric RNA. Thus, we suggest that primers and probes for nucleic acid detection should be designed in the middle of virus genome to identify live virus with higher probability. In summary, we propose our hypothesis that coronavirus invades human cells and interacts with retrotransposon, eliciting more severe symptoms in patients with underlying diseases. In the treatment of patients with coronavirus infection, it may be necessary to pay more attention to the potential harm contributed by retrotransposon dysregulation.


Assuntos
Infecções por Coronavirus/virologia , Coronavirus/genética , Genoma Viral/genética , Retroelementos/genética , Transcriptoma , Linhagem Celular Tumoral , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Vírus da SARS/genética , /genética
2.
J Biosci ; 462021.
Artigo em Inglês | MEDLINE | ID: mdl-33709963

RESUMO

SARS-CoV-2 is a member of the Coronavirus family which recently originated from the Wuhan province of China and spread very rapidly through the world infecting more than 4 million people. In the past, other Coronaviruses have also been found to cause human infection, but not as widespread as COVID-19. Since Coronavirus sequences constantly change due to mutation and recombination, it is important to understand the pattern of changes and likely path the virus can take in the future. In this study, we have used the Shewhart control chart to identify and analyze hypervariable (hotspots) and hypovariable (coldspots) regions of the virus. Our analysis shows that SARS-CoV-2 has changed in a few regions of the genome. Analysis of SARS-CoV-1 and MERS sequences suggests that over time, mutations start accumulating in different regions and most likely SARS-CoV-2 may also follow a similar path. The results suggest a possible emergence of modified viruses over some time.


Assuntos
Variação Genética , Genoma Viral , /genética , China , Genômica/métodos , Genômica/estatística & dados numéricos , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Polimorfismo de Nucleotídeo Único , Vírus da SARS/genética , Proteínas Virais/genética
3.
Artif Cells Nanomed Biotechnol ; 49(1): 204-218, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33645342

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoo tonic, highly pathogenic virus. The new type of coronavirus with contagious nature spread from Wuhan (China) to the whole world in a very short time and caused the new coronavirus disease (COVID-19). COVID-19 has turned into a global public health crisis due to spreading by close person-to-person contact with high transmission capacity. Thus, research about the treatment of the damages caused by the virus or prevention from infection increases everyday. Besides, there is still no approved and definitive, standardized treatment for COVID-19. However, this disaster experienced by human beings has made us realize the significance of having a system ready for use to prevent humanity from viral attacks without wasting time. As is known, nanocarriers can be targeted to the desired cells in vitro and in vivo. The nano-carrier system targeting a specific protein, containing the enzyme inhibiting the action of the virus can be developed. The system can be used by simple modifications when we encounter another virus epidemic in the future. In this review, we present a potential treatment method consisting of a nanoparticle-ribozyme conjugate, targeting ACE-2 receptors by reviewing the virus-associated ribozymes, their structures, types and working mechanisms.


Assuntos
/tratamento farmacológico , Nanopartículas/administração & dosagem , RNA Catalítico/uso terapêutico , RNA Viral/antagonistas & inibidores , /efeitos dos fármacos , /antagonistas & inibidores , Ensaios Clínicos como Assunto , Portadores de Fármacos , Composição de Medicamentos , Desenho de Fármacos , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Modelos Moleculares , Conformação de Ácido Nucleico , Interferência de RNA , RNA Catalítico/administração & dosagem , RNA Catalítico/química , RNA Catalítico/classificação , RNA não Traduzido/classificação , RNA não Traduzido/genética , RNA não Traduzido/uso terapêutico , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/genética , /fisiologia , Glicoproteína da Espícula de Coronavírus/fisiologia , Replicação Viral/efeitos dos fármacos
4.
J Vet Sci ; 22(1): e12, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33522164

RESUMO

BACKGROUND: Bats have been considered natural reservoirs for several pathogenic human coronaviruses (CoVs) in the last two decades. Recently, a bat CoV was detected in the Republic of Korea; its entire genome was sequenced and reported to be genetically similar to that of the severe acute respiratory syndrome CoV (SARS-CoV). OBJECTIVES: The objective of this study was to compare the genetic sequences of SARS-CoV, SARS-CoV-2, and the two Korean bat CoV strains 16BO133 and B15-21, to estimate the likelihood of an interaction between the Korean bat CoVs and the human angiotensin-converting enzyme 2 (ACE2) receptor. METHODS: The phylogenetic analysis was conducted with the maximum-likelihood (ML) method using MEGA 7 software. The Korean bat CoVs receptor binding domain (RBD) of the spike protein was analyzed by comparative homology modeling using the SWISS-MODEL server. The binding energies of the complexes were calculated using PRODIGY and MM/GBGA. RESULTS: Phylogenetic analyses of the entire RNA-dependent RNA polymerase, spike regions, and the complete genome revealed that the Korean CoVs, along with SARS-CoV and SARS-CoV-2, belong to the subgenus Sarbecovirus, within BetaCoVs. However, the two Korean CoVs were distinct from SARS-CoV-2. Specifically, the spike gene of the Korean CoVs, which is involved in host infection, differed from that of SARS-CoV-2, showing only 66.8%-67.0% nucleotide homology and presented deletions within the RBD, particularly within regions critical for cross-species transmission and that mediate interaction with ACE2. Binding free energy calculation revealed that the binding affinity of Korean bat CoV RBD to hACE2 was drastically lower than that of SARS-CoV and SARS-CoV-2. CONCLUSIONS: These results suggest that Korean bat CoVs are unlikely to bind to the human ACE2 receptor.


Assuntos
Quirópteros/virologia , Coronavirus/genética , Vírus da SARS/genética , /genética , Animais , Genes Virais/genética , Genoma Viral/genética , Genômica , Humanos , Funções Verossimilhança , Filogenia , Receptor Tipo 2 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/metabolismo , República da Coreia , Análise de Sequência de DNA , Homologia de Sequência , Glicoproteína da Espícula de Coronavírus/genética , Ligação Viral
5.
Cell Rep ; 34(7): 108737, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33545052

RESUMO

In the ongoing coronavirus disease 2019 (COVID-19) pandemic, there remain unanswered questions regarding the nature and significance of the humoral immune response toward other coronavirus infections. Here, we investigate the cross-reactivity of antibodies raised against the first severe acute respiratory syndrome coronavirus (SARS-CoV) for their reactivity toward SARS-CoV-2. We extensively characterize a selection of 10 antibodies covering all of the SARS-CoV structural proteins: spike, membrane, nucleocapsid, and envelope. Although nearly all of the examined SARS-CoV antibodies display some level of reactivity to SARS-CoV-2, we find only partial cross-neutralization for the spike antibodies. The implications of our work are two-fold. First, we establish a set of antibodies with known reactivity to both SARS-CoV and SARS-CoV-2, which will allow further study of both viruses. Second, we provide empirical evidence of the high propensity for antibody cross-reactivity between distinct strains of human coronaviruses, which is critical information for designing diagnostic and vaccine strategies for COVID-19.


Assuntos
Anticorpos Antivirais/imunologia , Vírus da SARS/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , /imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Células HEK293 , Humanos , Imunidade Humoral/imunologia , Pandemias , Vírus da SARS/genética , Glicoproteína da Espícula de Coronavírus/genética
6.
PLoS One ; 16(2): e0246901, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33596252

RESUMO

The MERS-CoV, SARS-CoV, and SARS-CoV-2 are highly pathogenic viruses that can cause severe pneumonic diseases in humans. Unfortunately, there is a non-available effective treatment to combat these viruses. Domain-motif interactions (DMIs) are an essential means by which viruses mimic and hijack the biological processes of host cells. To disentangle how viruses achieve this process can help to develop new rational therapies. Data mining was performed to obtain DMIs stored as regular expressions (regexp) in 3DID and ELM databases. The mined regexp information was mapped on the coronaviruses' proteomes. Most motifs on viral protein that could interact with human proteins are shared across the coronavirus species, indicating that molecular mimicry is a common strategy for coronavirus infection. Enrichment ontology analysis for protein domains showed a shared biological process and molecular function terms related to carbon source utilization and potassium channel regulation. Some of the mapped motifs were nested on B, and T cell epitopes, suggesting that it could be as an alternative way for reverse vaccinology. The information obtained in this study could be used for further theoretic and experimental explorations on coronavirus infection mechanism and development of medicines for treatment.


Assuntos
Betacoronavirus/metabolismo , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Mimetismo Molecular/fisiologia , Domínios e Motivos de Interação entre Proteínas/imunologia , Betacoronavirus/genética , /virologia , Infecções por Coronavirus/genética , Bases de Dados Genéticas , Interações Hospedeiro-Patógeno , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Domínios Proteicos , Domínios e Motivos de Interação entre Proteínas/genética , Proteoma , Vírus da SARS/genética , Vírus da SARS/metabolismo , /metabolismo , Proteínas Virais/metabolismo
7.
Sci Rep ; 11(1): 4108, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602998

RESUMO

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.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/genética , Infecções por Coronavirus/virologia , Códon/genética , Uso do Códon , Biologia Computacional/métodos , Coronavirus/genética , Infecções por Coronavirus/metabolismo , Genes Virais , Genoma Viral , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Filogenia , Vírus da SARS/genética , /genética
8.
Infect Genet Evol ; 88: 104708, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33421654

RESUMO

The pandemic due to novel coronavirus, SARS-CoV-2 is a serious global concern now. More than thousand new COVID-19 infections are getting reported daily for this virus across the globe. Thus, the medical research communities are trying to find the remedy to restrict the spreading of this virus, while the vaccine development work is still under research in parallel. In such critical situation, not only the medical research community, but also the scientists in different fields like microbiology, pharmacy, bioinformatics and data science are also sharing effort to accelerate the process of vaccine development, virus prediction, forecasting the transmissible probability and reproduction cases of virus for social awareness. With the similar context, in this article, we have studied sequence variability of the virus primarily focusing on three aspects: (a) sequence variability among SARS-CoV-1, MERS-CoV and SARS-CoV-2 in human host, which are in the same coronavirus family, (b) sequence variability of SARS-CoV-2 in human host for 54 different countries and (c) sequence variability between coronavirus family and country specific SARS-CoV-2 sequences in human host. For this purpose, as a case study, we have performed topological analysis of 2391 global genomic sequences of SARS-CoV-2 in association with SARS-CoV-1 and MERS-CoV using an integrated semi-alignment based computational technique. The results of the semi-alignment based technique are experimentally and statistically found similar to alignment based technique and computationally faster. Moreover, the outcome of this analysis can help to identify the nations with homogeneous SARS-CoV-2 sequences, so that same vaccine can be applied to their heterogeneous human population.


Assuntos
/epidemiologia , Infecções por Coronavirus/epidemiologia , Variação Genética , Genoma Viral , Pandemias , Síndrome Respiratória Aguda Grave/epidemiologia , África/epidemiologia , América/epidemiologia , Ásia/epidemiologia , Austrália/epidemiologia , Sequência de Bases , /virologia , Biologia Computacional/métodos , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Europa (Continente)/epidemiologia , Interações Hospedeiro-Patógeno/genética , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Vírus da SARS/genética , Vírus da SARS/patogenicidade , Alinhamento de Sequência , Síndrome Respiratória Aguda Grave/transmissão , Síndrome Respiratória Aguda Grave/virologia
9.
Biochem Biophys Res Commun ; 538: 24-34, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33413979

RESUMO

Two pandemics of respiratory distress diseases associated with zoonotic introductions of the species Severe acute respiratory syndrome-related coronavirus in the human population during 21st century raised unprecedented interest in coronavirus research and assigned it unseen urgency. The two viruses responsible for the outbreaks, SARS-CoV and SARS-CoV-2, respectively, are in the spotlight, and SARS-CoV-2 is the focus of the current fast-paced research. Its foundation was laid down by studies of many corona- and related viruses that collectively form the vast order Nidovirales. Comparative genomics of nidoviruses played a key role in this advancement over more than 30 years. It facilitated the transfer of knowledge from characterized to newly identified viruses, including SARS-CoV and SARS-CoV-2, as well as contributed to the dissection of the nidovirus proteome and identification of patterns of variations between different taxonomic groups, from species to families. This review revisits selected cases of protein conservation and variation that define nidoviruses, illustrates the remarkable plasticity of the proteome during nidovirus adaptation, and asks questions at the interface of the proteome and processes that are vital for nidovirus reproduction and could inform the ongoing research of SARS-CoV-2.


Assuntos
Infecções por Coronaviridae/virologia , Nidovirales/classificação , Nidovirales/genética , Sequência Conservada , Evolução Molecular , Variação Genética , Genômica , Humanos , Filogenia , Proteoma , Vírus da SARS/classificação , Vírus da SARS/genética , /genética , Proteínas Virais
10.
Emerg Microbes Infect ; 10(1): 196-205, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33399028

RESUMO

ABSTRACT Following outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2002 and 2012, respectively, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third highly pathogenic emerging human coronavirus (hCoV). SARS-CoV-2 is currently causing the global coronavirus disease 2019 (COVID-19) pandemic. CoV infections in target cells may stimulate the formation of numerous double-membrane autophagosomes and induce autophagy. Several studies provided evidence that hCoV infections are closely related to various cellular aspects associated with autophagy. Autophagy may even promote hCoV infection and replication. However, so far it is unclear how hCoV infections induce autophagy and whether the autophagic machinery is necessary for viral propagation. Here, we summarize the most recent advances concerning the mutual interplay between the autophagic machinery and the three emerging hCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 and the model system mouse hepatitis virus. We also discuss the applicability of approved and well-tolerated drugs targeting autophagy as a potential treatment against COVID-19.


Assuntos
Autofagossomos/virologia , Autofagia , /patogenicidade , Animais , Ensaios Clínicos como Assunto , Genoma Viral , Humanos , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Vírus da Hepatite Murina/patogenicidade , Vírus da SARS/genética , Vírus da SARS/patogenicidade , Internalização do Vírus/efeitos dos fármacos
11.
FASEB J ; 35(1): e21197, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33368679

RESUMO

SARS-CoV and SARS-CoV-2 encode four structural and accessory proteins (spike, envelope, membrane and nucleocapsid proteins) and two polyproteins (pp1a and pp1ab). The polyproteins are further cleaved by 3C-like cysteine protease (3CLpro ) and papain-like protease (PLpro ) into 16 nonstructural proteins (nsps). PLpro is released from nsp3 through autocleavage, and then it cleaves the sites between nsp1/2, between nsp2/3 and between nsp3/4 with recognition motif of LXGG, and the sites in the C-terminus of ubiquitin and of protein interferon-stimulated gene 15 (ISG15) with recognition motif of RLRGG. Alone or together with SARS unique domain (SUD), PLpro can stabilize an E3 ubiquitin ligase, the ring-finger, and CHY zinc-finger domain-containing 1 (RCHY1), through domain interaction, and thus, promote RCHY1 to ubiquitinate its target proteins including p53. However, a dilemma appears in terms of PLpro roles. On the one hand, the ubiquitination of p53 is good for SARS-CoV because the ubiquitinated p53 cannot inhibit SARS-CoV replication. On the other hand, the ubiquitination of NF-κB inhibitor (IκBα), TNF receptor-associated factors (TRAFs), and stimulator of interferon gene (STING), and the ISGylation of targeted proteins are bad for SARS-CoV because these ubiquitination and ISGylation initiate the innate immune response and antiviral state. This mini-review analyzes the dilemma and provides a snapshot on how the viral PLpro smartly manages its roles to avoid its simultaneously contradictory actions, which could shed lights on possible strategies to deal with SARS-CoV-2 infections.


Assuntos
/virologia , Vírus da SARS/fisiologia , Síndrome Respiratória Aguda Grave/virologia , /imunologia , /genética , Genes Virais , Interações Hospedeiro-Patógeno , Humanos , Terapia de Alvo Molecular , NF-kappa B/metabolismo , Domínios Proteicos , Processamento de Proteína Pós-Traducional , Vírus da SARS/genética , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/terapia , Especificidade por Substrato , Enzimas Ativadoras de Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Proteínas Virais/metabolismo , Replicação Viral
12.
Sci Rep ; 10(1): 22366, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33353955

RESUMO

Corona Virus Disease 2019 (COVID-19) caused by the emerged coronavirus SARS-CoV-2 is spreading globally. The origin of SARS-Cov-2 and its evolutionary relationship is still ambiguous. Several reports attempted to figure out this critical issue by genome-based phylogenetic analysis, yet limited progress was obtained, principally owing to the disability of these methods to reasonably integrate phylogenetic information from all genes of SARS-CoV-2. Supertree method based on multiple trees can produce the overall reasonable phylogenetic tree. However, the supertree method has been barely used for phylogenetic analysis of viruses. Here we applied the matrix representation with parsimony (MRP) pseudo-sequence supertree analysis to study the origin and evolution of SARS-CoV-2. Compared with other phylogenetic analysis methods, the supertree method showed more resolution power for phylogenetic analysis of coronaviruses. In particular, the MRP pseudo-sequence supertree analysis firmly disputes bat coronavirus RaTG13 be the last common ancestor of SARS-CoV-2, which was implied by other phylogenetic tree analysis based on viral genome sequences. Furthermore, the discovery of evolution and mutation in SARS-CoV-2 was achieved by MRP pseudo-sequence supertree analysis. Taken together, the MRP pseudo-sequence supertree provided more information on the SARS-CoV-2 evolution inference relative to the normal phylogenetic tree based on full-length genomic sequences.


Assuntos
/virologia , Quirópteros/virologia , Taxa de Mutação , Filogenia , /genética , Sequência de Aminoácidos , Animais , Genoma Viral , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Vírus da SARS/genética , Síndrome Respiratória Aguda Grave/virologia
13.
PLoS One ; 15(12): e0244025, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33351847

RESUMO

Coronaviruses such as SARS-CoV-2 regularly infect host tissues that express antiviral proteins (AVPs) in abundance. Understanding how they evolve to adapt or evade host immune responses is important in the effort to control the spread of infection. Two AVPs that may shape viral genomes are the zinc finger antiviral protein (ZAP) and the apolipoprotein B mRNA editing enzyme-catalytic polypeptide-like 3 (APOBEC3). The former binds to CpG dinucleotides to facilitate the degradation of viral transcripts while the latter frequently deaminates C into U residues which could generate notable viral sequence variations. We tested the hypothesis that both APOBEC3 and ZAP impose selective pressures that shape the genome of an infecting coronavirus. Our investigation considered a comprehensive number of publicly available genomes for seven coronaviruses (SARS-CoV-2, SARS-CoV, and MERS infecting Homo sapiens, Bovine CoV infecting Bos taurus, MHV infecting Mus musculus, HEV infecting Sus scrofa, and CRCoV infecting Canis lupus familiaris). We show that coronaviruses that regularly infect tissues with abundant AVPs have CpG-deficient and U-rich genomes; whereas those that do not infect tissues with abundant AVPs do not share these sequence hallmarks. Among the coronaviruses surveyed herein, CpG is most deficient in SARS-CoV-2 and a temporal analysis showed a marked increase in C to U mutations over four months of SARS-CoV-2 genome evolution. Furthermore, the preferred motifs in which these C to U mutations occur are the same as those subjected to APOBEC3 editing in HIV-1. These results suggest that both ZAP and APOBEC3 shape the SARS-CoV-2 genome: ZAP imposes a strong CpG avoidance, and APOBEC3 constantly edits C to U. Evolutionary pressures exerted by host immune systems onto viral genomes may motivate novel strategies for SARS-CoV-2 vaccine development.


Assuntos
/genética , Coronavirus/genética , Citidina Desaminase/genética , Proteínas de Ligação a RNA/genética , Proteínas Repressoras/genética , Animais , /virologia , Bovinos , Coronavirus/classificação , Coronavirus/patogenicidade , Cães , Evolução Molecular , Genoma Viral/genética , Humanos , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Vírus da SARS/genética , Vírus da SARS/patogenicidade , /patogenicidade , Suínos/virologia
15.
Front Immunol ; 11: 552909, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013925

RESUMO

The 2019 novel coronavirus (SARS-CoV-2) pandemic has caused a global health emergency. The outbreak of this virus has raised a number of questions: What is SARS-CoV-2? How transmissible is SARS-CoV-2? How severely affected are patients infected with SARS-CoV-2? What are the risk factors for viral infection? What are the differences between this novel coronavirus and other coronaviruses? To answer these questions, we performed a comparative study of four pathogenic viruses that primarily attack the respiratory system and may cause death, namely, SARS-CoV-2, severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and influenza A viruses (H1N1 and H3N2 strains). This comparative study provides a critical evaluation of the origin, genomic features, transmission, and pathogenicity of these viruses. Because the coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 is ongoing, this evaluation may inform public health administrators and medical experts to aid in curbing the pandemic's progression.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/epidemiologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Pneumonia Viral/epidemiologia , Vírus da SARS/genética , Síndrome Respiratória Aguda Grave/epidemiologia , Animais , Betacoronavirus/patogenicidade , Aves/virologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Genoma Viral , Humanos , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H3N2/patogenicidade , Influenza Aviária/epidemiologia , Influenza Aviária/transmissão , Influenza Aviária/virologia , Influenza Humana/transmissão , Influenza Humana/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/transmissão , Síndrome Respiratória Aguda Grave/virologia , Virulência/imunologia
16.
Sci Rep ; 10(1): 16944, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037310

RESUMO

The Spike protein of the novel coronavirus SARS-CoV2 contains an insertion 680SPRRAR↓SV687 forming a cleavage motif RxxR for furin-like enzymes at the boundary of S1/S2 subunits. Cleavage at S1/S2 is important for efficient viral entry into target cells. The insertion is absent in other CoV-s of the same clade, including SARS-CoV1 that caused the 2003 outbreak. However, an analogous cleavage motif was present at S1/S2 of the Spike protein of the more distant Middle East Respiratory Syndrome coronavirus MERS-CoV. We show that a crucial third arginine at the left middle position, comprising a motif RRxR is required for furin recognition in vitro, while the general motif RxxR in common with MERS-CoV is not sufficient for cleavage. Further, we describe a surprising finding that the two serines at the edges of the insert SPRRAR↓SV can be efficiently phosphorylated by proline-directed and basophilic protein kinases. Both phosphorylations switch off furin's ability to cleave the site. Although phospho-regulation of secreted proteins is still poorly understood, further studies, supported by a recent report of ten in vivo phosphorylated sites in the Spike protein of SARS-CoV2, could potentially uncover important novel regulatory mechanisms for SARS-CoV2.


Assuntos
Betacoronavirus/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Vírus da SARS/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Motivos de Aminoácidos/genética , Sequência de Aminoácidos , Furina/metabolismo , Fosforilação , Proteólise , Glicoproteína da Espícula de Coronavírus/genética , Internalização do Vírus
17.
Clin Microbiol Rev ; 34(1)2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33055229

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, introduced the third highly pathogenic coronavirus into humans in the 21st century. Scientific advance after the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic and Middle East respiratory syndrome coronavirus (MERS-CoV) emergence enabled clinicians to understand the epidemiology and pathophysiology of SARS-CoV-2. In this review, we summarize and discuss the epidemiology, clinical features, and virology of and host immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2 and the pathogenesis of coronavirus-induced acute respiratory distress syndrome (ARDS). We especially highlight that highly pathogenic coronaviruses might cause infection-associated hemophagocytic lymphohistiocytosis, which is involved in the immunopathogenesis of human coronavirus-induced ARDS, and also discuss the potential implication of hemophagocytic lymphohistiocytosis therapeutics for combating severe coronavirus infection.


Assuntos
Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/epidemiologia , Linfo-Histiocitose Hemofagocítica/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Betacoronavirus/genética , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/fisiopatologia , Interações Hospedeiro-Patógeno , Humanos , Período de Incubação de Doenças Infecciosas , Pulmão/imunologia , Pulmão/fisiopatologia , Pulmão/virologia , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Filogenia , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Vírus da SARS/genética , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/fisiopatologia , Índice de Gravidade de Doença , Análise de Sobrevida
18.
Hum Immunol ; 81(10-11): 588-595, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32888767

RESUMO

Coronavirus Disease 2019 (COVID-19) is a dangerous global threat that has no clinically approved treatment yet. Bioinformatics represent an outstanding approach to reveal key immunogenic regions in viral proteins. Here, five severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural proteins (NSPs) (NSP7, NSP8, NSP9, NSP12, and NSP13) were screened to identify potential human leukocyte antigen (HLA) binding peptides. These peptides showed robust viral antigenicity, immunogenicity, and a marked interaction with HLA alleles. Interestingly, several peptides showed affinity by HLA class I (HLA-I) alleles that commonly activates to natural killer (NK) cells. Notably, HLA biding peptides are conserved among SARS-CoV-2, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). Interestingly, HLA-I and HLA class II (HLA-II) binding peptides induced humoral and cell-mediated responses after in silico vaccination. These results may open further in vitro and in vivo investigations to develop novel therapeutic strategies against coronaviral infections.


Assuntos
Betacoronavirus/imunologia , Sequência Conservada/imunologia , Infecções por Coronavirus/imunologia , Antígenos HLA/imunologia , Pneumonia Viral/imunologia , Proteínas não Estruturais Virais/imunologia , Sequência de Aminoácidos , Betacoronavirus/genética , Infecções por Coronavirus/sangue , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Antígenos HLA/metabolismo , Humanos , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Vírus da SARS/genética , Vírus da SARS/imunologia , Vacinas de Subunidades/imunologia , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Vacinas Virais/imunologia
19.
Cell Death Dis ; 11(9): 799, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973152

RESUMO

A severe upper respiratory tract syndrome caused by the new coronavirus has now spread to the entire world as a highly contagious pandemic. The large scale explosion of the disease is conventionally traced back to January of this year in the Chinese province of Hubei, the wet markets of the principal city of Wuhan being assumed to have been the specific causative locus of the sudden explosion of the infection. A number of findings that are now coming to light show that this interpretation of the origin and history of the pandemic is overly simplified. A number of variants of the coronavirus would in principle have had the ability to initiate the pandemic well before January of this year. However, even if the COVID-19 had become, so to say, ready, conditions in the local environment would have had to prevail to induce the loss of the biodiversity's "dilution effect" that kept the virus under control, favoring its spillover from its bat reservoir to the human target. In the absence of these appropriate conditions only abortive attempts to initiate the pandemic could possibly occur: a number of them did indeed occur in China, and probably elsewhere as well. These conditions were unfortunately present at the wet marked in Wuhan at the end of last year.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/epidemiologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Animais , Betacoronavirus/classificação , Betacoronavirus/genética , Quirópteros/virologia , Infecções por Coronavirus/transmissão , Eutérios/virologia , Humanos , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Filogenia , Pneumonia Viral/transmissão , Ligação Proteica , Vírus da SARS/classificação , Vírus da SARS/genética , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Síndrome Respiratória Aguda Grave/transmissão , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Viverridae/virologia
20.
OMICS ; 24(11): 634-644, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32940573

RESUMO

In the first quarter of the 21st century, we are already facing the third emergence of a coronavirus outbreak, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the coronavirus disease 2019 (COVID-19) pandemic. Comparative genomics can inform a deeper understanding of the pathogenesis of COVID-19. Previous strains of coronavirus, SARS-CoV, and Middle-East respiratory syndrome-coronavirus (MERS-CoV), have been known to cause acute lung injuries in humans. SARS-CoV-2 shares genetic similarity with SARS-CoV with some modification in the S protein leading to their enhanced binding affinity toward the angiotensin-converting enzyme 2 (ACE2) receptors of human lung cells. This expert review examines the features of all three coronaviruses through a conceptual lens of comparative genomics. In particular, the life cycle of SARS-CoV-2 that enables its survival within the host is highlighted. Susceptibility of humans to coronavirus outbreaks in the 21st century calls for comparisons of the transmission history, hosts, reservoirs, and fatality rates of these viruses so that evidence-based and effective planetary health interventions can be devised to prevent future zoonotic outbreaks. Comparative genomics offers new insights on putative and novel viral targets with an eye to both therapeutic innovation and prevention. We conclude the expert review by (1) articulating the lessons learned so far, whereas the research is still being actively sought after in the field, and (2) the challenges and prospects in deciphering the linkages among multiomics biological variability and COVID-19 pathogenesis.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Genômica/métodos , Pandemias , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Animais , Betacoronavirus/genética , Quirópteros/virologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Eutérios/virologia , Saúde Global/tendências , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Ligação Proteica , Receptores Virais/genética , Receptores Virais/metabolismo , Vírus da SARS/genética , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Análise de Sobrevida
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