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1.
Immunity ; 54(5): 1055-1065.e5, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33945786

RESUMO

Efforts are being made worldwide to understand the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, including the impact of T cell immunity and cross-recognition with seasonal coronaviruses. Screening of SARS-CoV-2 peptide pools revealed that the nucleocapsid (N) protein induced an immunodominant response in HLA-B7+ COVID-19-recovered individuals that was also detectable in unexposed donors. A single N-encoded epitope that was highly conserved across circulating coronaviruses drove this immunodominant response. In vitro peptide stimulation and crystal structure analyses revealed T cell-mediated cross-reactivity toward circulating OC43 and HKU-1 betacoronaviruses but not 229E or NL63 alphacoronaviruses because of different peptide conformations. T cell receptor (TCR) sequencing indicated that cross-reactivity was driven by private TCR repertoires with a bias for TRBV27 and a long CDR3ß loop. Our findings demonstrate the basis of selective T cell cross-reactivity for an immunodominant SARS-CoV-2 epitope and its homologs from seasonal coronaviruses, suggesting long-lasting protective immunity.


Assuntos
Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Epitopos Imunodominantes/imunologia , SARS-CoV-2/imunologia , Sequência de Aminoácidos , Coronavirus/classificação , Coronavirus/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/química , Reações Cruzadas , Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Antígeno HLA-B7/química , Antígeno HLA-B7/genética , Antígeno HLA-B7/imunologia , Humanos , Epitopos Imunodominantes/química , Memória Imunológica , Modelos Moleculares , Peptídeos/química , Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia
2.
Viruses ; 13(4)2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915875

RESUMO

Coronavirus (CoV) spillover events from wildlife reservoirs can result in mild to severe human respiratory illness. These spillover events underlie the importance of detecting known and novel CoVs circulating in reservoir host species and determining CoV prevalence and distribution, allowing improved prediction of spillover events or where a human-reservoir interface should be closely monitored. To increase the likelihood of detecting all circulating genera and strains, we have modified primers published by Watanabe et al. in 2010 to generate a semi-nested pan-CoV PCR assay. Representatives from the four coronavirus genera (α-CoVs, ß-CoVs, γ-CoVs and δ-CoVs) were tested and all of the in-house CoVs were detected using this assay. After comparing both assays, we found that the updated assay reliably detected viruses in all genera of CoVs with high sensitivity, whereas the sensitivity of the original assay was lower. Our updated PCR assay is an important tool to detect, monitor and track CoVs to enhance viral surveillance in reservoir hosts.


Assuntos
Coronavirus/classificação , Coronavirus/genética , Coronavirus/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Animais , Animais Selvagens , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/virologia , Reservatórios de Doenças/virologia , Genoma Viral , Especificidade de Hospedeiro , Humanos , Limite de Detecção , Pandemias , Filogenia , RNA Viral
3.
Viruses ; 13(4)2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33920821

RESUMO

Coronaviruses (CoV) are widely distributed pathogens of human and animals and can cause mild or severe respiratory and gastrointestinal disease. Antigenic and genetic similarity of some CoVs within the Betacoronavirus genus is evident. Therefore, for the first time in Slovenia, we investigated the genetic diversity of partial 390-nucleotides of RNA-dependent-RNA polymerase gene (RdRp) for 66 human (HCoV) and 24 bovine CoV (BCoV) positive samples, collected between 2010 and 2016 from human patients and cattle with respiratory disease. The characterized CoV strains belong to four different clusters, in three separate human clusters HCoV-HKU1 (n = 34), HCoV-OC43 (n = 31) and HCoV 229E (n = 1) and bovine grouping only as BCoVs (n = 24). BCoVs from cattle and HCoV-OC43 were genetically the most closely related and share 96.4-97.1% nucleotide and 96.9-98.5% amino acid identity.


Assuntos
Doenças dos Bovinos/virologia , Coronavirus/classificação , Coronavirus/genética , Animais , Bovinos , Doenças dos Bovinos/transmissão , Coronavirus Humano 229E/genética , Infecções por Coronavirus/transmissão , Coronavirus Humano OC43/genética , Coronavirus Bovino/genética , Feminino , Variação Genética , Humanos , Masculino , Eslovênia
4.
Mol Biol Rep ; 48(4): 3629-3635, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33893925

RESUMO

PCR Single-Strand Conformation Polymorphism is a method used to identify and detect mutations and is now well known for its many applications on living beings. This paper will discuss the experimental details, limitations and sensitivity of the PCR Single-Strand Conformation Polymorphism method in relation to all existing literature available to us until today. Genomic DNA extraction, PCR amplification and Single-Strand Conformation Polymorphism conditions (concentration of polyacrylamide slab gel electrophoresis, dissociation treatment of double- stranded DNA) and comparison with PCR Restriction Fragment Length Polymorphism are presented. Since its discovery in 1989, there have been many variations, innovations, and modifications of the method, which makes it very easy, safe, fast and for this reason widely applied in clinical diagnostic, forensic medicine, biochemical, veterinary, microbiological, food and environmental laboratories. One of the possible applications of the method is the diagnosis and identification of mutations in new strains of coronaviruses, because science needs more tools to tackle the problem of this pandemic. The PCR Single-Strand Conformation Polymorphism method can be applied in many cases provided that control samples are available and the required conditions of the method are achieved.


Assuntos
Reação em Cadeia da Polimerase/métodos , Polimorfismo Conformacional de Fita Simples , Animais , Coronavirus/classificação , Coronavirus/genética , Coronavirus/isolamento & purificação , Humanos , Tipagem Molecular/métodos , Patologia Molecular/métodos , Polimorfismo de Fragmento de Restrição , Análise de Sequência/métodos
5.
Nature ; 592(7854): 340-343, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33854246
6.
Infect Dis Poverty ; 10(1): 28, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726861

RESUMO

BACKGROUND: Coronaviruses (CoVs) are distributed worldwide and have various susceptible hosts; CoVs infecting humans are called human coronaviruses (HCoVs). Although HCoV-specific drugs are still lacking, many potent targets for drug discovery are being explored, and many vigorously designed clinical trials are being carried out in an orderly manner. The aim of this review was to gain a comprehensive understanding of the current status of drug development against HCoVs, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MAIN TEXT: A scoping review was conducted by electronically searching research studies, reviews, and clinical trials in PubMed and the CNKI. Studies on HCoVs and therapeutic drug discovery published between January 2000 and October 2020 and in English or Chinese were included, and the information was summarized. Of the 3248 studies identified, 159 publication were finally included. Advances in drug development against HCoV, especially SARS-CoV-2, are summarized under three categories: antiviral drugs aimed at inhibiting the HCoV proliferation process, drugs acting on the host's immune system, and drugs derived from plants with potent activity. Furthermore, clinical trials of drugs targeting SARS-CoV-2 are summarized. CONCLUSIONS: During the spread of COVID-19 outbreak, great efforts have been made in therapeutic drug discovery against the virus, although the pharmacological effects and adverse reactions of some drugs under study are still unclear. However, well-designed high-quality studies are needed to further study the effectiveness and safety of these potential drugs so as to provide valid recommendations for better control of the COVID-19 pandemic.


Assuntos
Antivirais/farmacologia , Infecções por Coronavirus/virologia , Coronavirus/efeitos dos fármacos , Coronavirus/fisiologia , Descoberta de Drogas , Antivirais/uso terapêutico , Biomarcadores , COVID-19/tratamento farmacológico , COVID-19/metabolismo , COVID-19/virologia , Coronavirus/classificação , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Desenvolvimento de Medicamentos , Descoberta de Drogas/métodos , Regulação Viral da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Medicina Tradicional , Terapia de Alvo Molecular , SARS-CoV-2/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
7.
Bol Med Hosp Infant Mex ; 78(1): 41-58, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33661875

RESUMO

Coronaviruses (CoV) are enveloped, plus-strand RNA viruses that have the largest known RNA genomes and infect birds and mammals, causing various diseases. Human coronaviruses (HCoVs) were first identified in the mid-1960s and have been known to cause enteric or respiratory infections. In the last two decades, three HCoVs have emerged, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initiated the ongoing pandemic. SARS-CoV-2 causes a respiratory illness that presents as a mild upper respiratory disease but may result in acute respiratory distress syndrome, multi-organ failure and can be fatal, especially when underlying comorbidities are present. Children account for a low percentage of coronavirus disease 2019 (COVID-19) cases, with seemingly less severe disease. Most pediatric patients present mild or moderate symptoms or are asymptomatic. However, some cases may be severe. Therefore, SARS-CoV-2 infection and COVID-19 in pediatric patients must be studied in detail. This review describes general features of the molecular biology of CoVs and virus-host interactions that may be implicated in the pathogenesis of SARS-CoV-2.


Assuntos
COVID-19/virologia , Infecções por Coronavirus/virologia , Coronavirus/genética , Animais , COVID-19/epidemiologia , Criança , Coronavirus/classificação , Coronavirus/isolamento & purificação , Infecções por Coronavirus/classificação , Infecções por Coronavirus/epidemiologia , Humanos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
8.
Nature ; 593(7859): 418-423, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33727703

RESUMO

The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) in 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine-an anti-leprosy drug with a favourable safety profile3-possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and-when combined with remdesivir-in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and-possibly more importantly-in dealing with coronavirus diseases that may emerge in the future.


Assuntos
Antivirais/farmacologia , Clofazimina/farmacologia , Coronavirus/classificação , Coronavirus/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/farmacologia , Alanina/uso terapêutico , Animais , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antivirais/farmacocinética , Antivirais/uso terapêutico , Disponibilidade Biológica , Fusão Celular , Linhagem Celular , Clofazimina/farmacocinética , Clofazimina/uso terapêutico , Coronavirus/crescimento & desenvolvimento , Coronavirus/patogenicidade , Cricetinae , DNA Helicases/antagonistas & inibidores , Sinergismo Farmacológico , Feminino , Humanos , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Mesocricetus , Profilaxia Pré-Exposição , SARS-CoV-2/crescimento & desenvolvimento , Especificidade da Espécie , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Transcrição Genética/efeitos dos fármacos , Transcrição Genética/genética
9.
Infect Genet Evol ; 90: 104751, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33540085

RESUMO

COVID-19 is the currently evolving viral disease worldwide. It mainly targets the respiratory organs, tissues and causes illness. A plethora of studies has been performing to bring proper treatment and prevent people from the infection. Likewise, susceptibility to some infectious diseases has been associated with blood group phenotypes. The co-relationship of blood group with the occurrence of SARS-CoV-2 infection and death has been examined in numerous studies. This review explained the described studies regarding the correlation of blood group and the other essential factors with COVID-19.


Assuntos
Sistema ABO de Grupos Sanguíneos/genética , COVID-19/epidemiologia , COVID-19/etiologia , Suscetibilidade a Doenças , Fenótipo , SARS-CoV-2 , Sistema ABO de Grupos Sanguíneos/química , Sistema ABO de Grupos Sanguíneos/imunologia , Sistema ABO de Grupos Sanguíneos/metabolismo , Coronavirus/classificação , Coronavirus/imunologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Ligação Proteica , Receptores Virais/química , Receptores Virais/metabolismo , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Relação Estrutura-Atividade , Tromboplastina/metabolismo , Fator de von Willebrand/metabolismo
10.
Onderstepoort J Vet Res ; 88(1): e1-e8, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33567843

RESUMO

Human coronaviruses are known respiratory pathogens associated with a range of respiratory illnesses, and there are considerable morbidity and hospitalisation amongst immune-compromised individuals of all age groups. The emergence of a highly pathogenic human coronavirus in China in 2019 has confirmed the long-held opinion that these viruses are important emerging and re-emerging pathogens. In this review article, we trace the discovery and emergence of coronaviruses (CoVs) over time since they were first reported. The review article will enrich our understanding on the host range, diversity and evolution, transmission of human CoVs and the threat posed by these viruses circulating in animal populations but overtime have spilled over to humans because of the increased proximity between humans and animals.


Assuntos
Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/virologia , Coronavirus/classificação , Animais , Coronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Surtos de Doenças , Especificidade de Hospedeiro , Humanos
11.
Viruses ; 13(2)2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525437

RESUMO

The establishment of selective colonies of potential vertebrate hosts for viruses would provide experimental models for the understanding of pathogen-host interactions. This paper briefly surveys the reasons to conduct such studies and how the results might provide information that could be applied to disease prevention activities.


Assuntos
Reservatórios de Doenças/virologia , Interações Hospedeiro-Patógeno , Animais , COVID-19/prevenção & controle , COVID-19/transmissão , COVID-19/virologia , Quirópteros/virologia , Coronavirus/classificação , Coronavirus/genética , Coronavirus/patogenicidade , Especificidade de Hospedeiro , Humanos , SARS-CoV-2/classificação , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , Zoonoses/prevenção & controle , Zoonoses/virologia
12.
J Clin Invest ; 131(7)2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33571169

RESUMO

SARS-CoV-2 (CoV2) antibody therapies, including COVID-19 convalescent plasma (CCP), monoclonal antibodies, and hyperimmune globulin, are among the leading treatments for individuals with early COVID-19 infection. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the 4 endemic human coronavirus (HCoV) genomes in 126 CCP donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies against CoV2. We also found that plasma preferentially reactive to the CoV2 spike receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a 2-peptide serosignature that identifies plasma donations with high anti-spike titer, but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting desired therapeutics and understanding the complex immune responses elicited by CoV2 infection.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/imunologia , COVID-19/terapia , COVID-19/virologia , Coronavirus/imunologia , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/sangue , Especificidade de Anticorpos , Coronavirus/classificação , Coronavirus/genética , Reações Cruzadas , Doenças Endêmicas , Genoma Viral , Humanos , Imunização Passiva , Epitopos Imunodominantes/química , Epitopos Imunodominantes/genética , Epitopos Imunodominantes/imunologia , Modelos Moleculares , Pandemias , SARS-CoV-2/genética , Especificidade da Espécie , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia
13.
Viruses ; 13(2)2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530620

RESUMO

COVID-19 is a severe acute respiratory syndrome (SARS) caused by a new coronavirus (CoV), SARS-CoV-2, which is closely related to SARS-CoV that jumped the animal-human species barrier and caused a disease outbreak in 2003. SARS-CoV-2 is a betacoronavirus that was first described in 2019, unrelated to the commonly occurring feline coronavirus (FCoV) that is an alphacoronavirus associated with feline infectious peritonitis (FIP). SARS-CoV-2 is highly contagious and has spread globally within a few months, resulting in the current pandemic. Felids have been shown to be susceptible to SARS-CoV-2 infection. Particularly in the Western world, many people live in very close contact with their pet cats, and natural infections of cats in COVID-19-positive households have been described in several countries. In this review, the European Advisory Board on Cat Diseases (ABCD), a scientifically independent board of experts in feline medicine from 11 European Countries, discusses the current status of SARS-CoV infections in cats. The review examines the host range of SARS-CoV-2 and human-to-animal transmissions, including infections in domestic and non-domestic felids, as well as mink-to-human/-cat transmission. It summarises current data on SARS-CoV-2 prevalence in domestic cats and the results of experimental infections of cats and provides expert opinions on the clinical relevance and prevention of SARS-CoV-2 infection in cats.


Assuntos
COVID-19/transmissão , COVID-19/veterinária , Gatos/virologia , Animais , COVID-19/epidemiologia , COVID-19/virologia , Coronavirus/classificação , Coronavirus/isolamento & purificação , Coronavirus/patogenicidade , Especificidade de Hospedeiro , Humanos , Vison/virologia , Prevalência , SARS-CoV-2/classificação , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Zoonoses/epidemiologia , Zoonoses/prevenção & controle , Zoonoses/virologia
14.
mBio ; 12(1)2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419872

RESUMO

In December 2019 a new coronavirus (CoV) emerged as a human pathogen, SARS-CoV-2. There are few data on human coronavirus infections among individuals living with HIV. In this study we probed the role of pneumococcal coinfections with seasonal CoVs among children living with and without HIV hospitalized for pneumonia. We also described the prevalence and clinical manifestations of these infections. A total of 39,836 children who participated in a randomized, double-blind, placebo-controlled clinical trial on the efficacy of a 9-valent pneumococcal conjugate vaccine (PCV9) were followed for lower respiratory tract infection hospitalizations until 2 years of age. Nasopharyngeal aspirates were collected at the time of hospitalization and were screened by PCR for four seasonal CoVs. The frequency of CoV-associated pneumonia was higher in children living with HIV (19.9%) than in those without HIV (7.6%, P < 0.001). Serial CoV infections were detected in children living with HIV. The case fatality risk among children with CoV-associated pneumonia was higher in those living with HIV (30.4%) than without HIV (2.9%, P = 0.001). C-reactive protein and procalcitonin levels were elevated in 36.8% (≥40 mg/liter) and 64.7% (≥0.5 ng/ml), respectively, of the fatal cases living with HIV. Among children without HIV, there was a 64.0% (95% CI: 22.9% to 83.2%) lower incidence of CoV-associated pneumonia hospitalizations among PCV9 recipients compared to placebo recipients. These data suggest that Streptococcus pneumoniae infections might have a role in the development of pneumonia associated with endemic CoVs, that PCV may prevent pediatric CoV-associated hospitalization, and that children living with HIV with CoV infections develop more severe outcomes.IMPORTANCE SARS-CoV-2 may cause severe hospitalization, but little is known about the role of secondary bacterial infection in these severe cases, beyond the observation of high levels of reported inflammatory markers, associated with bacterial infection, such as procalcitonin. We did a secondary analysis of a double-blind randomized trial of PCV to examine its impact on human CoV infections before the pandemic. We found that both children living with and without HIV randomized to receive PCV had evidence of less hospitalization due to seasonal CoV, suggesting that pneumococcal coinfection may play a role in severe hospitalized CoV infections.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Infecções por Coronavirus/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Pneumonia Viral/prevenção & controle , Streptococcus pneumoniae/imunologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/patologia , Coinfecção/epidemiologia , Coinfecção/microbiologia , Coinfecção/prevenção & controle , Coinfecção/virologia , Coronavirus/classificação , Coronavirus/isolamento & purificação , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Lactente , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Pneumonia Viral/epidemiologia , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
mBio ; 12(1)2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468694

RESUMO

Among the animal superfamily Musteloidea, which includes those commonly known as mustelids, naturally occurring and species-specific alphacoronavirus infections have been observed in both mink (Mustela vison / Neovison vison) and domestic ferrets (Mustela putorius furo). Ferret systemic coronavirus (FRSCV), in particular, has been associated with a rare but fatal systemic disease. In recent months, it has become apparent that both minks and ferrets are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a betacoronavirus and the cause of the coronavirus disease 2019 (COVID-19) pandemic. Several mink farms have experienced SARS-CoV-2 outbreaks, and experimental models have demonstrated susceptibility of ferrets to SARS-CoV-2. The potential for pet ferrets to become infected with SARS-CoV-2, however, remains elusive. During the 2002-2003 SARS epidemic, it was also apparent that ferrets were susceptible to SARS-CoV and could be utilized in vaccine development. From a comparative standpoint, understanding the relationships between different infections and disease pathogenesis in the animal superfamily Musteloidea may help elucidate viral infection and transmission mechanisms, as well as treatment and prevention strategies for coronaviruses.


Assuntos
Caniformia/virologia , Infecções por Coronavirus/veterinária , Coronavirus/classificação , Animais , COVID-19/veterinária , COVID-19/virologia , Coronavirus/isolamento & purificação , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Surtos de Doenças/veterinária , Suscetibilidade a Doenças , Fazendas , Filogenia , SARS-CoV-2/isolamento & purificação , Especificidade da Espécie
16.
J Virol ; 95(6)2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33443088

RESUMO

Developing optimal T-cell response assays to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is critical for measuring the duration of immunity to this disease and assessing the efficacy of vaccine candidates. These assays need to target conserved regions of SARS-CoV-2 global variants and avoid cross-reactivity to seasonal human coronaviruses. To contribute to this effort, we employed an in silico immunoinformatics analysis pipeline to identify immunogenic peptides resulting from conserved and highly networked regions with topological importance from the SARS-CoV-2 nucleocapsid and spike proteins. A total of 57 highly networked T-cell epitopes that are conserved across geographic viral variants were identified from these viral proteins, with a binding potential to diverse HLA alleles and 80 to 100% global population coverage. Importantly, 18 of these T-cell epitope derived peptides had limited homology to seasonal human coronaviruses making them promising candidates for SARS-CoV-2-specific T-cell immunity assays. Moreover, two of the NC-derived peptides elicited effector/polyfunctional responses of CD8+ T cells derived from SARS-CoV-2 convalescent patients.IMPORTANCE The development of specific and validated immunologic tools is critical for understanding the level and duration of the cellular response induced by SARS-CoV-2 infection and/or vaccines against this novel coronavirus disease. To contribute to this effort, we employed an immunoinformatics analysis pipeline to define 57 SARS-CoV-2 immunogenic peptides within topologically important regions of the nucleocapsid (NC) and spike (S) proteins that will be effective for detecting cellular immune responses in 80 to 100% of the global population. Our immunoinformatics analysis revealed that 18 of these peptides had limited homology to circulating seasonal human coronaviruses and therefore are promising candidates for distinguishing SARS-CoV-2-specific immune responses from pre-existing coronavirus immunity. Importantly, CD8+ T cells derived from SARS-CoV-2 survivors exhibited polyfunctional effector responses to two novel NC-derived peptides identified as HLA-binders. These studies provide a proof of concept that our immunoinformatics analysis pipeline identifies novel immunogens which can elicit polyfunctional SARS-CoV-2-specific T-cell responses.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Epitopos de Linfócito T/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Sequência de Aminoácidos , Apresentação do Antígeno , COVID-19/sangue , COVID-19/imunologia , Biologia Computacional , Coronavirus/classificação , Coronavirus/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/química , Proteínas do Nucleocapsídeo de Coronavírus/genética , Epitopos de Linfócito T/química , Epitopos de Linfócito T/genética , Antígenos HLA/imunologia , Humanos , Imunidade Celular , Mutação , Fosfoproteínas/química , Fosfoproteínas/genética , Fosfoproteínas/imunologia , Ligação Proteica , SARS-CoV-2/genética , Especificidade da Espécie , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética
17.
BMC Med ; 19(1): 19, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33430856

RESUMO

BACKGROUND: Cross-reactivity to SARS-CoV-2 from exposure to endemic human coronaviruses (eHCoV) is gaining increasing attention as a possible driver of both protection against infection and COVID-19 severity. Here we explore the potential role of cross-reactivity induced by eHCoVs on age-specific COVID-19 severity in a mathematical model of eHCoV and SARS-CoV-2 transmission. METHODS: We use an individual-based model, calibrated to prior knowledge of eHCoV dynamics, to fully track individual histories of exposure to eHCoVs. We also model the emergent dynamics of SARS-CoV-2 and the risk of hospitalisation upon infection. RESULTS: We hypothesise that primary exposure with any eHCoV confers temporary cross-protection against severe SARS-CoV-2 infection, while life-long re-exposure to the same eHCoV diminishes cross-protection, and increases the potential for disease severity. We show numerically that our proposed mechanism can explain age patterns of COVID-19 hospitalisation in EU/EEA countries and the UK. We further show that some of the observed variation in health care capacity and testing efforts is compatible with country-specific differences in hospitalisation rates under this model. CONCLUSIONS: This study provides a "proof of possibility" for certain biological and epidemiological mechanisms that could potentially drive COVID-19-related variation across age groups. Our findings call for further research on the role of cross-reactivity to eHCoVs and highlight data interpretation challenges arising from health care capacity and SARS-CoV-2 testing.


Assuntos
COVID-19 , Infecções por Coronavirus , Proteção Cruzada/imunologia , Reações Cruzadas/imunologia , SARS-CoV-2/imunologia , Fatores Etários , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/fisiopatologia , Coronavirus/classificação , Coronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Doenças Endêmicas , Hospitalização/estatística & dados numéricos , Humanos , Imunidade Heteróloga/imunologia , Modelagem Computacional Específica para o Paciente , Índice de Gravidade de Doença
18.
Cell ; 184(2): 476-488.e11, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33412089

RESUMO

Coronavirus disease 2019 (COVID-19) exhibits variable symptom severity ranging from asymptomatic to life-threatening, yet the relationship between severity and the humoral immune response is poorly understood. We examined antibody responses in 113 COVID-19 patients and found that severe cases resulting in intubation or death exhibited increased inflammatory markers, lymphopenia, pro-inflammatory cytokines, and high anti-receptor binding domain (RBD) antibody levels. Although anti-RBD immunoglobulin G (IgG) levels generally correlated with neutralization titer, quantitation of neutralization potency revealed that high potency was a predictor of survival. In addition to neutralization of wild-type SARS-CoV-2, patient sera were also able to neutralize the recently emerged SARS-CoV-2 mutant D614G, suggesting cross-protection from reinfection by either strain. However, SARS-CoV-2 sera generally lacked cross-neutralization to a highly homologous pre-emergent bat coronavirus, WIV1-CoV, which has not yet crossed the species barrier. These results highlight the importance of neutralizing humoral immunity on disease progression and the need to develop broadly protective interventions to prevent future coronavirus pandemics.


Assuntos
Anticorpos Neutralizantes/imunologia , Biomarcadores/análise , COVID-19/imunologia , COVID-19/fisiopatologia , Adulto , Anticorpos Neutralizantes/análise , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Biomarcadores/sangue , COVID-19/sangue , COVID-19/epidemiologia , Comorbidade , Coronavirus/classificação , Coronavirus/fisiologia , Reações Cruzadas , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/análise , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Domínios Proteicos , SARS-CoV-2/química , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/química , Análise de Sobrevida , Resultado do Tratamento
19.
J Virol Methods ; 290: 114070, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33497729

RESUMO

Viral infections are one of the main cause of diseases worldwide due to the rising trends of migration, urbanization and global mobility of humans. The outbreak of corona virus diseases caused by SARS-CoV (year 2003), MERS-CoV (year 2012) and SARS-CoV-2 (year 2019) raised global health concerns. The side effects associated with the conventional drugs and increase in cases of anti-microbial resistance have led the researchers to switch to natural sources, especially plants, as they have immense potential to be used as antiviral agents. The aim of the article is to summarize the evidences of the bioactive phytocompounds from different plants as an effective alternative for the treatment of infections caused by coronaviruses. However, the use of most plant compounds succumbs to limitations due to lack of experimental evidences and safety studies. Therefore, further research and studies are required to validate their therapeutic uses for wide application of plant-based medicine, including anti-virals.


Assuntos
Antivirais/farmacologia , Infecções por Coronavirus/virologia , Coronavirus/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Antivirais/química , Antivirais/uso terapêutico , Coronavirus/classificação , Coronavirus/fisiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Genoma Viral , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêutico , Plantas Medicinais/química , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/metabolismo
20.
Public Health Genomics ; 24(1-2): 54-66, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33406522

RESUMO

INTRODUCTION: SARS-CoV-2 is a new type of coronavirus causing a pandemic severe acute respiratory syndrome (SARS-2). Coronaviruses are very diverting genetically and mutate so often periodically. The natural selection of viral mutations may cause host infection selectivity and infectivity. METHODS: This study was aimed to indicate the diversity between human and animal coronaviruses through finding the rate of mutation in each of the spike, nucleocapsid, envelope, and membrane proteins. RESULTS: The mutation rate is abundant in all 4 structural proteins. The most number of statistically significant amino acid mutations were found in spike receptor-binding domain (RBD) which may be because it is responsible for a corresponding receptor binding in a broad range of hosts and host selectivity to infect. Among 17 previously known amino acids which are important for binding of spike to angiotensin-converting enzyme 2 (ACE2) receptor, all of them are conservative among human coronaviruses, but only 3 of them significantly are mutated in animal coronaviruses. A single amino acid aspartate-454, that causes dissociation of the RBD of the spike and ACE2, and F486 which gives the strength of binding with ACE2 remain intact in all coronaviruses. DISCUSSION/CONCLUSION: Observations of this study provided evidence of the genetic diversity and rapid evolution of SARS-CoV-2 as well as other human and animal coronaviruses.


Assuntos
COVID-19/virologia , Coronavirus , Variação Genética/fisiologia , SARS-CoV-2 , Proteínas Virais , Animais , Coronavirus/classificação , Coronavirus/genética , Coronavirus/fisiologia , Evolução Molecular , Interações entre Hospedeiro e Microrganismos/genética , Humanos , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Proteínas Virais/genética , Proteínas Virais/metabolismo
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