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1.
Molecules ; 26(20)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34684763

RESUMO

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, the causative agent of coronavirus disease (COVID-19)) has caused relatively high mortality rates in humans throughout the world since its first detection in late December 2019, leading to the most devastating pandemic of the current century. Consequently, SARS-CoV-2 therapeutic interventions have received high priority from public health authorities. Despite increased COVID-19 infections, a vaccine or therapy to cover all the population is not yet available. Herein, immunoinformatics and custommune tools were used to identify B and T-cells epitopes from the available SARS-CoV-2 sequences spike (S) protein. In the in silico predictions, six B cell epitopes QTGKIADYNYK, TEIYQASTPCNGVEG, LQSYGFQPT, IRGDEVRQIAPGQTGKIADYNYKLPD, FSQILPDPSKPSKRS and PFAMQMAYRFNG were cross-reacted with MHC-I and MHC-II T-cells binding epitopes and selected for vaccination in experimental animals for evaluation as candidate vaccine(s) due to their high antigenic matching and conserved score. The selected six peptides were used individually or in combinations to immunize female Balb/c mice. The immunized mice raised reactive antibodies against SARS-CoV-2 in two different short peptides located in receptor binding domain and S2 region. In combination groups, an additive effect was demonstrated in-comparison with single peptide immunized mice. This study provides novel epitope-based peptide vaccine candidates against SARS-CoV-2.


Assuntos
Vacinas contra COVID-19/química , COVID-19/prevenção & controle , Epitopos de Linfócito B/química , Epitopos de Linfócito T/química , SARS-CoV-2/metabolismo , Sequência de Aminoácidos , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/metabolismo , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/metabolismo , Feminino , Humanos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/química , Peptídeos/imunologia , Peptídeos/metabolismo , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo
2.
Front Microbiol ; 12: 611958, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679636

RESUMO

Currently, all available antiviral drugs against influenza virus (IV) that target the virus proteins directly, like Baloxavir acid (BXA), lead to viral resistance. Therefore, cellular mechanisms and factors essential for IV replication are promising antiviral targets. As IV strongly depends on the virus-induced Raf/MEK/ERK signal pathway for efficient generation of infectious progeny virions, this pathway represents an important target. We aimed to determine whether the MEK inhibitor ATR-002 (PD0184264) is able to impair replication of BXA-resistant influenza A virus (IAV) and whether a treatment combining BXA and ATR-002 improves the therapeutic efficiency in vitro. A549 cells infected with different IAV strains including BXA-resistant variants were treated with ATR-002 or BXA and the effect on virus titer reduction was determined. The synergistic effect of ATR-002 and BXA was also analyzed using different evaluation methods. The data demonstrated that ATR-002 has a significant and dose-dependent inhibitory effect on IAV replication across different strains and subtypes. IAV with the PA-I38T mutation shows resistance against BXA, but is still susceptible toward ATR-002. The combination of ATR-002 and BXA exhibited a synergistic potency reflected by low combination index values. In conclusion, we show that ATR-002 permits to counteract the limitations of BXA against BXA-resistant IAV. Moreover, the results support the use of ATR-002 (i) in a mono-therapy, as well as (ii) in a combined approach together with BXA. These findings might also apply to the treatment of infections with IAV, resistant against other direct-acting antiviral compounds.

3.
Pathogens ; 8(4)2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810359

RESUMO

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) became a global human health threat since its first documentation in humans in 2012. An efficient vaccine for the prophylaxis of humans in hotspots of the infection (e.g., Saudi Arabia) is necessary but no commercial vaccines are yet approved. In this study, a chimeric DNA construct was designed to encode an influenza A/H1N1 NA protein which is flanking immunogenic amino acids (aa) 736-761 of MERS-CoV spike protein. Using the generated chimeric construct, a novel recombinant vaccine strain against pandemic influenza A virus (H1N1pdm09) and MERS-CoV was generated (chimeric bivalent 5 + 3). The chimeric bivalent 5 + 3 vaccine strain comprises a recombinant PR8-based vaccine, expressing the PB1, HA, and chimeric NA of pandemic 2009 H1N1. Interestingly, an increase in replication efficiency of the generated vaccine strain was observed when compared to the PR8-based 5 + 3 H1N1pdm09 vaccine strain that lacks the MERS-CoV spike peptide insert. In BALB/c mice, the inactivated chimeric bivalent vaccine induced potent and specific neutralizing antibodies against MERS-CoV and H1N1pdm09. This novel approach succeeded in developing a recombinant influenza virus with potential use as a bivalent vaccine against H1N1pdm09 and MERS-CoV. This approach provides a basis for the future development of chimeric influenza-based vaccines against MERS-CoV and other viruses.

4.
Viruses ; 11(8)2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31387326

RESUMO

: Dromedary camels are the natural reservoirs of the Middle East respiratory syndrome coronavirus (MERS-CoV). Camels are mostly bred in East African countries then exported into Africa and Middle East for consumption. To understand the distribution of MERS-CoV among camels in North Africa and the Middle East, we conducted surveillance in Egypt, Senegal, Tunisia, Uganda, Jordan, Saudi Arabia, and Iraq. We also performed longitudinal studies of three camel herds in Egypt and Jordan to elucidate MERS-CoV infection and transmission. Between 2016 and 2018, a total of 4027 nasal swabs and 3267 serum samples were collected from all countries. Real- time PCR revealed that MERS-CoV RNA was detected in nasal swab samples from Egypt, Senegal, Tunisia, and Saudi Arabia. Microneutralization assay showed that antibodies were detected in all countries. Positive PCR samples were partially sequenced, and a phylogenetic tree was built. The tree suggested that all sequences are of clade C and sequences from camels in Egypt formed a separate group from previously published sequences. Longitudinal studies showed high seroprevalence in adult camels. These results indicate the widespread distribution of the virus in camels. A systematic active surveillance and longitudinal studies for MERS-CoV are needed to understand the epidemiology of the disease and dynamics of viral infection.


Assuntos
Camelus/virologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/classificação , África/epidemiologia , Animais , Anticorpos Antivirais/sangue , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Reservatórios de Doenças/virologia , Estudos Longitudinais , Oriente Médio/epidemiologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Filogenia , Vigilância da População , Estudos Soroepidemiológicos
6.
Vaccines (Basel) ; 7(2)2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31141982

RESUMO

Vaccination is the most functional medical intervention to prophylactically control severe diseases caused by human-to-human or animal-to-human transmissible viral pathogens. Annually, seasonal influenza epidemics attack human populations leading to 290-650 thousand deaths/year worldwide. Recently, a novel Middle East Respiratory Syndrome Coronavirus emerged. Together, those two viruses present a significant public health burden in areas where they circulate. Herein, we generated a bacterial outer membrane vesicles (OMVs)-based vaccine presenting the antigenic stable chimeric fusion protein of the H1-type haemagglutinin (HA) of the pandemic influenza A virus (H1N1) strain from 2009 (H1N1pdm09) and the receptor binding domain (RBD) of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) (OMVs-H1/RBD). Our results showed that the chimeric antigen could induce specific neutralizing antibodies against both strains leading to protection of immunized mice against H1N1pdm09 and efficient neutralization of MERS-CoV. This study demonstrate that OMVs-based vaccines presenting viral antigens provide a safe and reliable approach to protect against two different viral infections.

7.
J Virol ; 93(2)2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30381492

RESUMO

Recently, two genetically distinct influenza viruses were detected in bats in Guatemala and Peru. We conducted influenza A virus surveillance among four bat species in Egypt. Out of 1,202 swab specimens, 105 were positive by real-time PCR. A virus was successfully isolated in eggs and propagated in MDCK cells in the presence of N-tosyl-l-phenylalanine chloromethyl ketone-treated trypsin. Genomic analysis revealed that the virus was phylogenetically distinct from all other influenza A viruses. Analysis of the hemagglutinin gene suggested a common ancestry with other H9 viruses, and the virus showed a low level of cross-reactivity with serum raised against H9N2 viruses. Bats were seropositive for the isolated viruses. The virus replicated in the lungs of experimentally infected mice. While it is genetically distinct, this virus shares several avian influenza virus characteristics suggesting a more recent avian host origin.IMPORTANCE Through surveillance, we isolated and characterized an influenza A virus from Egyptian fruit bats. This virus had an affinity to avian-like receptors but was also able to infect mice. Our findings indicate that bats may harbor a diversity of influenza A viruses. Such viruses may have the potential to cross the species barrier to infect other species, including domestic birds, mammals, and, possibly, humans.


Assuntos
Quirópteros/virologia , Vírus da Influenza A/classificação , Infecções por Orthomyxoviridae/imunologia , RNA Viral/genética , Análise de Sequência de RNA/métodos , Animais , Anticorpos Antivirais/metabolismo , Galinhas , Cães , Egito , Vírus da Influenza A/genética , Vírus da Influenza A/isolamento & purificação , Pulmão/virologia , Células Madin Darby de Rim Canino , Infecções por Orthomyxoviridae/virologia , Filogenia
8.
Arch Virol ; 163(2): 359-364, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29075888

RESUMO

The majority of the Egyptian swine population was culled in the aftermath of the 2009 H1N1 pandemic, but small-scale growing remains. We sampled pigs from piggeries and an abattoir in Cairo. We found virological evidence of infection with avian H9N2 and H5N1 viruses as well as human pandemic H1N1 influenza virus. Serological evidence suggested previous exposure to avian H5N1 and H9N2, human pandemic H1N1, and swine avian-like and human-like viruses. This raises concern about potential reassortment of influenza viruses in pigs and highlights the need for better control and prevention of influenza virus infection in pigs.


Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Virus da Influenza A Subtipo H5N1/isolamento & purificação , Vírus da Influenza A Subtipo H9N2/isolamento & purificação , Influenza Aviária/virologia , Influenza Humana/virologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/virologia , Animais , Aves , Egito/epidemiologia , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Virus da Influenza A Subtipo H5N1/classificação , Virus da Influenza A Subtipo H5N1/genética , Vírus da Influenza A Subtipo H9N2/classificação , Vírus da Influenza A Subtipo H9N2/genética , Influenza Aviária/epidemiologia , Influenza Humana/epidemiologia , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/virologia , Filogenia , Vírus Reordenados/classificação , Vírus Reordenados/genética , Vírus Reordenados/isolamento & purificação , Suínos , Doenças dos Suínos/epidemiologia
9.
Emerg Microbes Infect ; 6(1): e1, 2017 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-28050021

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe human infections and dromedary camels are considered an intermediary host. The dynamics of natural infection in camels are not well understood. Through systematic surveillance in Egypt, nasal, rectal, milk, urine and serum samples were collected from camels between June 2014 and February 2016. Locations included quarantines, markets, abattoirs, free-roaming herds and farmed breeding herds. The overall seroprevalence was 71% and RNA detection rate was 15%. Imported camels had higher seroprevalence (90% vs 61%) and higher RT-PCR detection rates (21% vs 12%) than locally raised camels. Juveniles had lower seroprevalence than adults (37% vs 82%) but similar RT-PCR detection rates (16% vs 15%). An outbreak in a breeding herd, showed that antibodies rapidly wane, that camels become re-infected, and that outbreaks in a herd are sustained for an extended time. Maternal antibodies titers were very low in calves regardless of the antibody titers of the mothers. Our results support the hypothesis that camels are a reservoir for MERS-CoV and that camel trade is an important route of introducing the virus into importing countries. Findings related to waning antibodies and re-infection have implications for camel vaccine development, disease management and zoonotic threat.


Assuntos
Camelus/virologia , Infecções por Coronavirus/veterinária , Monitoramento Epidemiológico , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Técnicas de Diagnóstico Molecular , Testes Sorológicos , Animais , Anticorpos Antivirais/sangue , Líquidos Corporais/virologia , Bovinos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Egito/epidemiologia , Feminino , Masculino , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Mucosa Nasal/virologia , RNA Viral/análise , Reto/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estudos Soroepidemiológicos
10.
Genome Announc ; 4(2)2016 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-27125484

RESUMO

We generated the near-full genome sequence of Middle East respiratory syndrome coronavirus (MERS-CoV) from a collected nasal sample of dromedary camel in Egypt. The newly characterized Egyptian strain has high similarity to the previously characterized Egyptian virus and both of viruses fell into a cluster distinct from other MERS-CoVs.

11.
Front Med ; 10(2): 120-36, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26791756

RESUMO

The Middle East respiratory syndrome coronavirus was first identified in 2012 and has since then remained uncontrolled. Cases have been mostly reported in the Middle East, however travel-associated cases and outbreaks have also occurred. Nosocomial and zoonotic transmission of the virus appear to be the most important routes. The infection is severe and highly fatal thus necessitating rapid and efficacious interventions. Here, we performed a comprehensive review of published literature and summarized the epidemiology of the virus. In addition, we summarized the virological aspects of the infection and reviewed the animal models used as well as vaccination and antiviral tested against it.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecção Hospitalar/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Viagem , Vacinação/métodos , Animais , Antivirais/uso terapêutico , Camelus , Quirópteros , Infecções por Coronavirus/tratamento farmacológico , Modelos Animais de Doenças , Surtos de Doenças , Furões , Humanos , Macaca mulatta , Mesocricetus , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/classificação , Coelhos , Estações do Ano , Vacinas/uso terapêutico
12.
Vaccine ; 34(2): 218-224, 2016 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-26620838

RESUMO

BACKGROUND: Avian influenza H5N1 viruses have been enzootic in Egyptian poultry since 2006. Avian influenza H9N2 viruses which have been circulating in Egyptian poultry since 2011 showed high replication rates in embryonated chicken eggs and mammalian cells. METHODS: To investigate which gene segment was responsible for increasing replication, we constructed reassortant influenza viruses using the low pathogenic H1N1 PR8 virus as backbone and included individual genes from A/chicken/Egypt/S4456B/2011(H9N2) virus. Then, we invested this finding to improve a PR8-derived H5N1 influenza vaccine strain by incorporation of the NA segment of H9N2 virus instead of the NA of H5N1. The growth properties of this virus and several other forms of reassortant H5 viruses were compared. Finally, we tested the efficacy of this reassortant vaccine strain in chickens. RESULTS: We observed an increase in replication for a reassortant virus expressing the neuraminidase gene (N2) of H9N2 virus relative to that of either parental viruses or reassortant PR8 viruses expressing other genes. Then, we generated an H5N2 vaccine strain based on the H5 from an Egyptian H5N1 virus and the N2 from an Egyptian H9N2 virus on a PR8 backbone. This strain had better replication rates than an H5N2 reassortant strain on an H9N2 backbone and an H5N1 reassortant on a PR8 backbone. This virus was then used to develop a killed, oil-emulsion vaccine and tested for efficacy against H5N1 and H9N2 viruses in chickens. Results showed that this vaccine was immunogenic and reduced mortality and shedding. DISCUSSION: Our findings suggest that an inactivated PR8-derived H5N2 influenza vaccine is efficacious in poultry against H5N1 and H9N2 viruses and the vaccine seed replicates at a high rate thus improving vaccine production.


Assuntos
Virus da Influenza A Subtipo H5N1/imunologia , Vírus da Influenza A Subtipo H5N2/imunologia , Vírus da Influenza A Subtipo H9N2/imunologia , Vacinas contra Influenza/imunologia , Influenza Aviária/prevenção & controle , Vírus Reordenados/imunologia , Animais , Galinhas , Egito , Virus da Influenza A Subtipo H5N1/genética , Vírus da Influenza A Subtipo H5N2/genética , Vírus da Influenza A Subtipo H9N2/genética , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Vacinas contra Influenza/isolamento & purificação , Vírus Reordenados/genética , Genética Reversa , Análise de Sobrevida , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/genética , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/isolamento & purificação , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/isolamento & purificação
14.
Arch Virol ; 159(11): 2861-76, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24990416

RESUMO

Avian influenza virus subtype H9N2 has been circulating in the Middle East since the 1990s. For uncertain reasons, H9N2 was not detected in Egyptian farms until the end of 2010. Circulation of H9N2 viruses in Egyptian poultry in the presence of the enzootic highly pathogenic H5N1 subtype adds a huge risk factor to the Egyptian poultry industry. In this study, 22 H9N2 viruses collected from 2011 to 2013 in Egypt were isolated and sequenced. The genomic signatures and protein sequences of these isolates were analyzed. Multiple mammalian-host-associated mutations were detected that favor transmission from avian to mammalian hosts. Other mutations related to virulence were also identified. Phylogenetic data showed that Egyptian H9N2 viruses were closely related to viruses isolated from neighboring Middle Eastern countries, and their HA gene resembled those of viruses of the G1-like lineage. No reassortment was detected with H5N1 subtypes. Serological analysis of H9N2 virus revealed antigenic conservation among Egyptian isolates. Accordingly, continuous surveillance that results in genetic and antigenic characterization of H9N2 in Egypt is warranted.


Assuntos
Antígenos Virais/genética , Evolução Molecular , Vírus da Influenza A Subtipo H9N2/genética , Vírus da Influenza A Subtipo H9N2/imunologia , Influenza Aviária/virologia , Doenças das Aves Domésticas/virologia , Proteínas Virais/genética , Sequência de Aminoácidos , Animais , Antígenos Virais/química , Antígenos Virais/imunologia , Egito/epidemiologia , Vírus da Influenza A Subtipo H9N2/classificação , Vírus da Influenza A Subtipo H9N2/isolamento & purificação , Influenza Aviária/epidemiologia , Dados de Sequência Molecular , Filogenia , Aves Domésticas , Doenças das Aves Domésticas/epidemiologia , Alinhamento de Sequência , Proteínas Virais/química , Proteínas Virais/imunologia
15.
Emerg Infect Dis ; 20(6): 1049-53, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24856660

RESUMO

We identified the near-full-genome sequence (29,908 nt, >99%) of Middle East respiratory syndrome coronavirus (MERS-CoV) from a nasal swab specimen from a dromedary camel in Egypt. We found that viruses genetically very similar to human MERS-CoV are infecting dromedaries beyond the Arabian Peninsula, where human MERS-CoV infections have not yet been detected.


Assuntos
Anticorpos Antivirais/sangue , Camelus/virologia , Infecções por Coronavirus/veterinária , Genoma Viral , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Proteínas Virais/genética , Matadouros , Adolescente , Adulto , Idoso , Animais , Portador Sadio , Criança , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Egito/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/classificação , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Filogenia
16.
Emerg Infect Dis ; 20(4): 542-51, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24655395

RESUMO

Continuous circulation of influenza A(H5N1) virus among poultry in Egypt has created an epicenter in which the viruses evolve into newer subclades and continue to cause disease in humans. To detect influenza viruses in Egypt, since 2009 we have actively surveyed various regions and poultry production sectors. From August 2010 through January 2013, >11,000 swab samples were collected; 10% were positive by matrix gene reverse transcription PCR. During this period, subtype H9N2 viruses emerged, cocirculated with subtype H5N1 viruses, and frequently co-infected the same avian host. Genetic and antigenic analyses of viruses revealed that influenza A(H5N1) clade 2.2.1 viruses are dominant and that all subtype H9N2 viruses are G1-like. Cocirculation of different subtypes poses concern for potential reassortment. Avian influenza continues to threaten public and animal health in Egypt, and continuous surveillance for avian influenza virus is needed.


Assuntos
Influenza Aviária/epidemiologia , Animais , Aves/virologia , Egito/epidemiologia , Virus da Influenza A Subtipo H5N1/genética , Vírus da Influenza A Subtipo H9N2/genética
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