Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Front Immunol ; 13: 816159, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35273599

RESUMO

During the ongoing COVID-19 epidemic many efforts have gone into the investigation of the SARS-CoV-2-specific antibodies as possible therapeutics. Currently, conclusions cannot be drawn due to the lack of standardization in antibody assessments. Here we describe an approach of establishing antibody characterisation in emergent times which would, if followed, enable comparison of results from different studies. The key component is a reliable and reproducible assay of wild-type SARS-CoV-2 neutralisation based on a banking system of its biological components - a challenge virus, cells and an anti-SARS-CoV-2 antibody in-house standard, calibrated to the First WHO International Standard immediately upon its availability. Consequently, all collected serological data were retrospectively expressed in an internationally comparable way. The neutralising antibodies (NAbs) among convalescents ranged from 4 to 2869 IU mL-1 in a significant positive correlation to the disease severity. Their decline in convalescents was on average 1.4-fold in a one-month period. Heat-inactivation resulted in 2.3-fold decrease of NAb titres in comparison to the native sera, implying significant complement activating properties of SARS-CoV-2 specific antibodies. The monitoring of NAb titres in the sera of immunocompromised COVID-19 patients that lacked their own antibodies evidenced the successful transfusion of antibodies by the COVID-19 convalescent plasma units with NAb titres of 35 IU mL-1 or higher.


Assuntos
COVID-19/terapia , Imunização Passiva/métodos , Testes de Neutralização/métodos , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/genética , COVID-19/epidemiologia , Calibragem , Células Cultivadas , Doenças Transmissíveis Emergentes , Convalescença , Proteases Semelhantes à Papaína de Coronavírus/genética , Proteases Semelhantes à Papaína de Coronavírus/imunologia , Croácia , Epidemias , Humanos , Cooperação Internacional , Padrões de Referência , Glicoproteína da Espícula de Coronavírus/imunologia , Resultado do Tratamento
2.
Molecules ; 27(2)2022 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-35056718

RESUMO

The advancements in the field of nanotechnology have provided a great platform for the development of effective antiviral vaccines. Liposome-mediated delivery of antigens has been shown to induce the antigen-specific stimulation of the humoral and cell-mediated immune responses. Here, we prepared dried, reconstituted vesicles (DRVs) from DPPC liposomes and used them as the vaccine carrier system for the Middle East respiratory syndrome coronavirus papain-like protease (DRVs-MERS-CoV PLpro). MERS-CoV PLpro emulsified in the Incomplete Freund's Adjuvant (IFA-MERS-CoV PLpro) was used as a control. Immunization of mice with DRVs-MERS-CoV PLpro did not induce any notable toxicity, as revealed by the levels of the serum alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) in the blood of immunized mice. Immunization with DRVs-MERS-CoV PLpro induced greater antigen-specific antibody titer and switching of IgG1 isotyping to IgG2a as compared to immunization with IFA-MERS-CoV PLpro. Moreover, splenocytes from mice immunized with DRVs-MERS-CoV PLpro exhibited greater proliferation in response to antigen stimulation. Moreover, splenocytes from DRVs-MERS-CoV PLpro-immunized mice secreted significantly higher IFN-γ as compared to splenocytes from IFA-MERS-CoV PLpro mice. In summary, DRVs-MERS-CoV PLpro may prove to be an effective prophylactic formulation to prevent MERS-CoV infection.


Assuntos
Proteases Semelhantes à Papaína de Coronavírus/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Animais , Proliferação de Células , Infecções por Coronavirus/prevenção & controle , Feminino , Imunidade Celular , Imunidade Humoral , Imunização/métodos , Imunoglobulina G/sangue , Interferon gama/metabolismo , Lipossomos/administração & dosagem , Lipossomos/química , Lipossomos/imunologia , Lipossomos/toxicidade , Linfócitos/metabolismo , Camundongos , Vacinas Virais/química , Vacinas Virais/toxicidade
3.
Scand J Immunol ; 94(4): e13044, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33872387

RESUMO

Coronaviruses (CoVs) are a large family of respiratory viruses which can cause mild to moderate upper respiratory tract infections. Recently, new coronavirus named as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified which is a major threat to public health. Innate immune responses play a vital role in a host's defence against viruses. Interestingly, CoVs have evolved elaborate strategies to evade the complex system of sensors and signalling molecules to suppress host immunity. SARS-CoV-2 papain-like protease (PLpro), as an important coronavirus enzyme, regulates viral spread and innate immune responses. SCoV-2 PLpro is multifunctional enzyme with deubiquitinating (DUB) and deISGylating activity. The PLpro can interact with key regulators in signalling pathways such as STING, NF-κB, cytokine production, MAPK and TGF-ß and hijack those to block the immune responses. Therefore, the PLpro can be as an important target for the treatment of COVID-19. Until now, several drugs or compounds have been identified that can inhibit PLpro activity. Here we discuss about the dysregulation effects of PLpro on immune system and drugs that have potential inhibitors for SCoV-2 PLpro.


Assuntos
COVID-19/imunologia , Proteases Semelhantes à Papaína de Coronavírus/imunologia , Sistema Imunitário/imunologia , SARS-CoV-2/imunologia , Proteínas Virais/imunologia , Antivirais/administração & dosagem , Antivirais/imunologia , COVID-19/virologia , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Sistema Imunitário/metabolismo , NF-kappa B/imunologia , NF-kappa B/metabolismo , Ligação Proteica/efeitos dos fármacos , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Proteínas Virais/metabolismo , Tratamento Farmacológico da COVID-19
4.
J Med Virol ; 93(9): 5350-5357, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33913542

RESUMO

PARP14 and PARP9 play a key role in macrophage immune regulation. SARS-CoV-2 is an emerging viral disease that triggers hyper-inflammation known as a cytokine storm. In this study, using in silico tools, we hypothesize about the immunological phenomena of molecular mimicry between SARS-CoV-2 Nsp3 and the human PARP14 and PARP9. The results showed an epitope of SARS-CoV-2 Nsp3 protein that contains consensus sequences for both human PARP14 and PARP9 that are antigens for MHC Classes 1 and 2, which can potentially induce an immune response against human PARP14 and PARP9; while its depletion causes a hyper-inflammatory state in SARS-CoV-2 patients.


Assuntos
COVID-19/imunologia , Proteases Semelhantes à Papaína de Coronavírus/química , Síndrome da Liberação de Citocina/imunologia , Proteínas de Neoplasias/química , Poli(ADP-Ribose) Polimerases/química , SARS-CoV-2/imunologia , Sequência de Aminoácidos , Sítios de Ligação , COVID-19/genética , COVID-19/patologia , COVID-19/virologia , Simulação por Computador , Sequência Consenso , Proteases Semelhantes à Papaína de Coronavírus/genética , Proteases Semelhantes à Papaína de Coronavírus/imunologia , Síndrome da Liberação de Citocina/genética , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/virologia , Epitopos/química , Epitopos/genética , Epitopos/imunologia , Expressão Gênica , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/química , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Macrófagos/imunologia , Macrófagos/virologia , Simulação de Acoplamento Molecular , Mimetismo Molecular , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/imunologia , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Termodinâmica
5.
Genes Immun ; 21(6-8): 409-419, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33273723

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading fast worldwide. There is a pressing need to understand how the virus counteracts host innate immune responses. Deleterious clinical manifestations of coronaviruses have been associated with virus-induced direct dysregulation of innate immune responses occurring via viral macrodomains located within nonstructural protein-3 (Nsp3). However, no substantial information is available concerning the relationship of macrodomains to the unusually high pathogenicity of SARS-CoV-2. Here, we show that structural evolution of macrodomains may impart a critical role to the unique pathogenicity of SARS-CoV-2. Using sequence, structural, and phylogenetic analysis, we identify a specific set of historical substitutions that recapitulate the evolution of the macrodomains that counteract host immune response. These evolutionary substitutions may alter and reposition the secondary structural elements to create new intra-protein contacts and, thereby, may enhance the ability of SARS-CoV-2 to inhibit host immunity. Further, we find that the unusual virulence of this virus is potentially the consequence of Darwinian selection-driven epistasis in protein evolution. Our findings warrant further characterization of macrodomain-specific evolutionary substitutions in in vitro and in vivo models to determine their inhibitory effects on the host immune system.


Assuntos
COVID-19 , Proteases Semelhantes à Papaína de Coronavírus , Evolução Molecular , Evasão da Resposta Imune , Filogenia , SARS-CoV-2 , COVID-19/genética , COVID-19/imunologia , Proteases Semelhantes à Papaína de Coronavírus/genética , Proteases Semelhantes à Papaína de Coronavírus/imunologia , Humanos , SARS-CoV-2/genética , SARS-CoV-2/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...