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1.
Biomedica ; 40(Supl. 2): 173-179, 2020 10 30.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33152201

RESUMO

Coronaviruses cause respiratory and gastrointestinal disorders in animals and humans. The current SARS-CoV-2, the COVID-19 infectious agent, belongs to a subgroup called betacoronavirus including the SARS-CoV and MERS-CoV responsible for epidemics in 2002 and 2012, respectively. These viruses can also infect the nervous system due to their affinity for the human angiotensin-converting enzyme 2 (ACE2) expressed in neurons and glial cells. Infections with SARS-CoV, MERS-CoV, and now SARS-CoV-2 also produce neurological signs such as acute cerebrovascular disease, impaired consciousness, and muscle injury, as well as dizziness, hypogeusia, hyposmia, hypoxia, neuralgia, and hypoxic encephalopathy. For this reason, close attention should be paid to the neurological manifestations of COVID-19 patients.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Doenças do Sistema Nervoso/etiologia , Pneumonia Viral/complicações , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/complicações , Líquido Cefalorraquidiano/virologia , Transtornos Cerebrovasculares/etiologia , Transtornos da Consciência/etiologia , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Previsões , Humanos , Doenças Musculoesqueléticas/etiologia , Pandemias , Pneumonia Viral/epidemiologia , Síndrome do Desconforto Respiratório do Adulto/etiologia , Transtornos das Sensações/etiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Latência Viral
2.
Clin Microbiol Rev ; 34(1)2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33055231

RESUMO

Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir (GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses. In vivo, remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Doença pelo Vírus Ebola/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Monofosfato de Adenosina/farmacocinética , Monofosfato de Adenosina/farmacologia , Alanina/farmacocinética , Alanina/farmacologia , Antivirais/farmacocinética , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/crescimento & desenvolvimento , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Ensaios de Uso Compassivo/métodos , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Esquema de Medicação , Ebolavirus/efeitos dos fármacos , Ebolavirus/crescimento & desenvolvimento , Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/mortalidade , Doença pelo Vírus Ebola/patologia , Doença pelo Vírus Ebola/virologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/crescimento & desenvolvimento , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Segurança do Paciente , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/crescimento & desenvolvimento , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/patologia , Síndrome Respiratória Aguda Grave/virologia , Análise de Sobrevida , Resultado do Tratamento
3.
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
4.
Rev. esp. quimioter ; 33(5): 313-326, oct. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-193704

RESUMO

ANTECEDENTES: La aparición de nuevas enfermedades infecciosas, como el COVID-19, supone un reto en el seguimiento de la gestación y la prevención de complicaciones obstétricas y neonatales. La revisión exploratoria tiene el objetivo de revisar la información disponible en mujeres embarazadas infectadas por los coronavirus MERS-CoV, SARS-CoV, SARS-CoV-2 para evaluar las similitudes y diferencias en las características clínicas de las madres y los resultados neonatales. MÉTODOS: Realizamos una búsqueda bibliográfica (revisión exploratoria) acorde a las pautas de PRISMA entre marzo y abril del 2020 en las bases de datos de MEDLINE, SciELO, y CUIDEN y el Centro de Información sobre el COVID-19 de Elsevier. RESULTADOS: Analizamos 20 artículos con un total de 102 casos: 9 de MERS-CoV, 14 de SARS-CoV y 79 de SARS-CoV-2. La fiebre (75,5%) y la neumonía (73,5%) resultaron ser los síntomas más frecuentes en las gestantes infectadas. Las complicaciones obstétricas más frecuentes fueron la amenaza de parto prematuro (23,5%) y la cesárea (74,5%). No se documentó ninguna transmisión vertical en los neonatos. CONCLUSIONES: Los tres coronavirus producen una neumonía con sintomatología muy similar, resultando más leve en el caso de SARS-CoV-2. A pesar de las complicaciones obstétricas documentadas, los resultados neonatales son favorables en su mayoría. Es preciso aumentar el conocimiento para mejorar y prevenir las complicaciones obstétricas y neonatales de estas infecciones en mujeres embarazadas


BACKGROUND: The appearance of new infectious diseases, such as COVID-19, poses a challenge in monitoring pregnancy and preventing obstetric and neonatal complications. A scoping review has the objective to review the information available in pregnant women infected with the MERS-CoV, SARSCoV, SARS-CoV-2 coronaviruses to assess the similarities in terms of and differences in the clinical characteristics of the mothers and neonatal outcomes. METHODS: We carried out a bibliographic search (scoping review) according to the PRISMA guidelines between March and April 2020 in the MEDLINE, SciELO, and CUIDEN databases and the Elsevier COVID-19 Information Center. RESULTS: We analyzed 20 articles with a total of 102 cases. 9 of MERS-CoV, 14 of SARS-CoV and 79 of SARS-CoV-2. Fever (75.5%) and pneumonia (73.5%) were the most frequent symptoms in infected pregnant women. The most frequent obstetric complications were the threat of premature delivery (23.5%) and caesarean section (74.5%). No vertical transmission was documented in any of the infants. CONCLUSIONS: All three coronaviruses produce pneumonia with very similar symptoms, being milder in the case of SARSCoV2. Despite documented obstetric complications, neonatal outcomes are mostly favorable. Increased knowledge is needed to improve and prevent obstetric and neonatal complications from these infections in pregnant women


Assuntos
Humanos , Complicações Infecciosas na Gravidez/epidemiologia , Infecções por Coronavirus/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Vírus da SARS/patogenicidade , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Pandemias/estatística & dados numéricos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade
5.
Signal Transduct Target Ther ; 5(1): 237, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051445

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named coronavirus disease (COVID-19). Currently, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Vaccines, such as inactivated vaccines, nucleic acid-based vaccines, and vector vaccines, have already entered clinical trials. In this review, we provide an overview of the experimental and clinical data obtained from recent SARS-CoV-2 vaccines trials, and highlight certain potential safety issues that require consideration when developing vaccines. Furthermore, we summarize several strategies utilized in the development of vaccines against other infectious viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), with the aim of aiding in the design of effective therapeutic approaches against SARS-CoV-2.


Assuntos
Anticorpos Antivirais/biossíntese , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Peptidil Dipeptidase A/genética , Pneumonia Viral/prevenção & controle , Receptores Virais/genética , Vacinas Virais/biossíntese , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imunidade Inata/efeitos dos fármacos , Esquemas de Imunização , Imunogenicidade da Vacina , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Segurança do Paciente , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Ligação Proteica , Receptores Virais/antagonistas & inibidores , Receptores Virais/metabolismo , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas Atenuadas , Vacinas de DNA , Vacinas de Subunidades , Vacinas de Partículas Semelhantes a Vírus , Vacinas Virais/administração & dosagem
6.
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
7.
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
8.
Eur J Med Res ; 25(1): 39, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887660

RESUMO

BACKGROUND: Coronavirus is challenging the global health care system from time to time. The pregnant state, with alterations in hormone levels and decreased lung volumes due to a gravid uterus and slightly immunocompromised state may predispose patients to a more rapidly deteriorating clinical course and can get a greater risk of harm for both the mother and fetus. Therefore, this systematic review was aimed to assess the effect of coronavirus infection (SARS-CoV-2, MERS-CoV, and SARS-CoV) during pregnancy and its possibility of vertical maternal-fetal transmission. METHODS: A systematic search was conducted on PubMed, Web of Science, Embase, Google Scholar and the Cochrane Library until the end of April. All authors independently extracted all necessary data using excel spreadsheet form. Only published articles with fully accessible data on pregnant women infected with SARS-CoV, MARS-CoV, and SARS-CoV-2 were included. Data on clinical manifestations, maternal and perinatal outcomes were extracted and analyzed. RESULT: Out of 879 articles reviewed, 39 studies involving 1316 pregnant women were included. The most common clinical features were fever, cough, and myalgia with prevalence ranging from 30 to 97%, while lymphocytopenia and C-reactive protein were the most common abnormal laboratory findings (55-100%). Pneumonia was the most diagnosed clinical symptom of COVID-19 and non-COVID-19 infection with prevalence ranged from 71 to 89%. Bilateral pneumonia (57.9%) and ground-glass opacity (65.8%) were the most common CT imaging reported. The most common treatment options used were hydroxychloroquine (79.7%), ribavirin (65.2%), and oxygen therapy (78.8%). Regarding maternal outcome, the rate of preterm birth < 37 weeks of gestation was 14.3%, preeclampsia (5.9%), miscarriage (14.5%, preterm premature rupture of membranes (9.2%) and fetal growth restriction (2.8%). From the total coronavirus infected pregnant women, 56.9% delivered by cesarean, 31.3% admitted to ICU, while 2.7% were died. Among the perinatal outcomes, fetal distress rated (26.5%), neonatal asphyxia rated (1.4%). Only, 1.2% of neonates had apgar score < 7 at 5 min. Neonate admitted to ICU was rated 11.3%, while the rate of perinatal death was 2.2%. In the current review, none of the studies reported transmission of CoV from the mother to the fetus in utero during the study period. CONCLUSION: Coronavirus infection is more likely to affect pregnant women. Respiratory infectious diseases have demonstrated an increased risk of adverse maternal obstetrical complications than the general population due to physiological changes occurred during pregnancy. None of the studies reported transmission of CoV from the mother to the fetus in utero, which may be due to a very low expression of angiotensin-converting enzyme-2 in early maternal-fetal interface cells.


Assuntos
Infecções por Coronavirus/transmissão , Transmissão Vertical de Doença Infecciosa , Pneumonia Viral/transmissão , Complicações Infecciosas na Gravidez/virologia , Síndrome Respiratória Aguda Grave/transmissão , Adolescente , Adulto , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/diagnóstico , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Síndrome Respiratória Aguda Grave/diagnóstico , Adulto Jovem
9.
Bratisl Lek Listy ; 121(10): 733-741, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32955906

RESUMO

Recent emergence of SARS-CoV-2 in human communities as the first major zoonotic pandemics of the new millennium following the emergence of SARS-CoV and MERS-CoV has increased our awareness about the future threat of viral zoonosis. Although, several studies have been conducted for better understanding of these viruses` evolution, and designing the effective anti-viral drugs and vaccines, the impact of human beings on occurrence of zoonotic diseases has been less considered and discussed. Improvement in global health resulted in human population growth, increasing demand for animal proteins, more exposures to wildlife, zoonotic and degradation of environment, which have facilitated interspecies transmissions. Since world population is increasing proportionately, the protection of public health against zoonotic diseases is a challenging task. It seems that intensified revision of human lifestyle is the best strategy to prevent the potential devastating future zoonotic pandemics. Herein, the characteristics of SARS-CoV, MERS-CoV, SARS-CoV-2, their transmission routs, their pathogenicity, the therapeutic and prevention approaches including of attempts for designing of effective prophylactic vaccines, anti-viral drugs, and the animal models that have been used for these studies have been reviewed (Ref. 134). Keywords: SARS-CoV-2, COVID-19, pandemic, zoonosis, SARS, MERS.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/transmissão , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Vírus da SARS/patogenicidade , Animais , Antivirais , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Modelos Animais de Doenças , Humanos , Pandemias , Pneumonia Viral , Vacinas Virais
10.
Molecules ; 25(18)2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899754

RESUMO

The emergence of the Coronavirus Disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has led to an unprecedented pandemic, which demands urgent development of antiviral drugs and antibodies; as well as prophylactic approaches, namely vaccines. Algae biotechnology has much to offer in this scenario given the diversity of such organisms, which are a valuable source of antiviral and anti-inflammatory compounds that can also be used to produce vaccines and antibodies. Antivirals with possible activity against SARS-CoV-2 are summarized, based on previously reported activity against Coronaviruses or other enveloped or respiratory viruses. Moreover, the potential of algae-derived anti-inflammatory compounds to treat severe cases of COVID-19 is contemplated. The scenario of producing biopharmaceuticals in recombinant algae is presented and the cases of algae-made vaccines targeting viral diseases is highlighted as valuable references for the development of anti-SARS-CoV-2 vaccines. Successful cases in the production of functional antibodies are described. Perspectives on how specific algae species and genetic engineering techniques can be applied for the production of anti-viral compounds antibodies and vaccines against SARS-CoV-2 are provided.


Assuntos
Antivirais/farmacologia , Produtos Biológicos/farmacologia , Chlamydomonas reinhardtii/genética , Infecções por Coronavirus/tratamento farmacológico , Lectinas/farmacologia , Pneumonia Viral/tratamento farmacológico , Polifenóis/farmacologia , Polissacarídeos/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Núcleo Celular/química , Núcleo Celular/genética , Núcleo Celular/metabolismo , Chlamydomonas reinhardtii/química , Chlamydomonas reinhardtii/metabolismo , Cloroplastos/química , Cloroplastos/genética , Cloroplastos/metabolismo , Infecções por Coronavirus/prevenção & controle , Engenharia Genética/métodos , Humanos , Lectinas/química , Lectinas/isolamento & purificação , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Polifenóis/química , Polifenóis/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Vacinas Virais/biossíntese , Vacinas Virais/farmacologia
11.
Biomolecules ; 10(9)2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32933047

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face a microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (severe acute respiratory syndrome (SARS-CoV) and middle east respiratory syndrome (MERS-CoV)) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans (HCoVs), which circulate continuously in the human population, but their phenotypes are generally mild, and these HCoVs received relatively little attention. These dramatic differences between infection with HCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 raise many questions, such as: Why is COVID-19 transmitted so quickly? Is it due to some specific features of the viral structure? Are there some specific human (host) factors? Are there some environmental factors? The aim of this review is to collect and concisely summarize the possible and logical answers to these questions.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/transmissão , Coronavirus/patogenicidade , Pandemias , Pneumonia Viral/transmissão , Fatores Etários , Animais , Betacoronavirus/genética , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Surtos de Doenças , Reservatórios de Doenças/virologia , Feminino , Saúde Global , Especificidade de Hospedeiro , Interações Hospedeiro-Patógeno , Humanos , Masculino , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Especificidade de Órgãos , Peptídeo Hidrolases/fisiologia , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Receptores Virais/fisiologia , Fatores de Risco , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/epidemiologia , Proteínas Virais/fisiologia , Tropismo Viral , Virulência , Internalização do Vírus
12.
Molecules ; 25(17)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867349

RESUMO

Three types of new coronaviruses (CoVs) have been identified recently as the causative viruses for the severe pneumonia-like respiratory illnesses, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and corona-virus disease 2019 (COVID-19). Neither therapeutic agents nor vaccines have been developed to date, which is a major drawback in controlling the present global pandemic of COVID-19 caused by SARS coronavirus 2 (SARS-CoV-2) and has resulted in more than 20,439,814 cases and 744,385 deaths. Each of the 3C-like (3CL) proteases of the three CoVs is essential for the proliferation of the CoVs, and an inhibitor of the 3CL protease (3CLpro) is thought to be an ideal therapeutic agent against SARS, MERS, or COVID-19. Among these, SARS-CoV is the first corona-virus isolated and has been studied in detail since the first pandemic in 2003. This article briefly reviews a series of studies on SARS-CoV, focusing on the development of inhibitors for the SARS-CoV 3CLpro based on molecular interactions with the 3CL protease. Our recent approach, based on the structure-based rational design of a novel scaffold for SARS-CoV 3CLpro inhibitor, is also included. The achievements summarized in this short review would be useful for the design of a variety of novel inhibitors for corona-viruses, including SARS-CoV-2.


Assuntos
Antivirais/química , Betacoronavirus/química , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Inibidores de Proteases/química , Vírus da SARS/patogenicidade , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/classificação , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/enzimologia , Domínio Catalítico , Infecções por Coronavirus/tratamento farmacológico , Cristalografia por Raios X , Cisteína Endopeptidases/química , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Humanos , Cinética , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteases/classificação , Inibidores de Proteases/uso terapêutico , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Vírus da SARS/genética , Vírus da SARS/metabolismo , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Especificidade por Substrato , Termodinâmica , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
13.
Hum Genomics ; 14(1): 30, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917282

RESUMO

The COVID-19 pandemic has strengthened the interest in the biological mechanisms underlying the complex interplay between infectious agents and the human host. The spectrum of phenotypes associated with the SARS-CoV-2 infection, ranging from the absence of symptoms to severe systemic complications, raised the question as to what extent the variable response to coronaviruses (CoVs) is influenced by the variability of the hosts' genetic background.To explore the current knowledge about this question, we designed a systematic review encompassing the scientific literature published from Jan. 2003 to June 2020, to include studies on the contemporary outbreaks caused by SARS-CoV-1, MERS-CoV and SARS-CoV-2 (namely SARS, MERS and COVID-19 diseases). Studies were eligible if human genetic variants were tested as predictors of clinical phenotypes.An ad hoc protocol for the rapid review process was designed according to the PRISMA paradigm and registered at the PROSPERO database (ID: CRD42020180860). The systematic workflow provided 32 articles eligible for data abstraction (28 on SARS, 1 on MERS, 3 on COVID-19) reporting data on 26 discovery cohorts. Most studies considered the definite clinical diagnosis as the primary outcome, variably coupled with other outcomes (severity was the most frequently analysed). Ten studies analysed HLA haplotypes (1 in patients with COVID-19) and did not provide consistent signals of association with disease-associated phenotypes. Out of 22 eligible articles that investigated candidate genes (2 as associated with COVID-19), the top-ranked genes in the number of studies were ACE2, CLEC4M (L-SIGN), MBL, MxA (n = 3), ACE, CD209, FCER2, OAS-1, TLR4, TNF-α (n = 2). Only variants in MBL and MxA were found as possibly implicated in CoV-associated phenotypes in at least two studies. The number of studies for each predictor was insufficient to conduct meta-analyses.Studies collecting large cohorts from different ancestries are needed to further elucidate the role of host genetic variants in determining the response to CoVs infection. Rigorous design and robust statistical methods are warranted.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/genética , Interações Hospedeiro-Patógeno/genética , Pneumonia Viral/genética , Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Variação Genética/genética , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Fenótipo , Pneumonia Viral/epidemiologia , Vírus da SARS/genética , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/genética
14.
Methods Mol Biol ; 2203: 1-29, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833200

RESUMO

Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, an unusually large RNA genome, and a unique replication strategy. CoVs cause a variety of diseases in mammals and birds ranging from enteritis in cows and pigs, and upper respiratory tract and kidney disease in chickens to lethal human respiratory infections. Most recently, the novel coronavirus, SARS-CoV-2, which was first identified in Wuhan, China in December 2019, is the cause of a catastrophic pandemic, COVID-19, with more than 8 million infections diagnosed worldwide by mid-June 2020. Here we provide a brief introduction to CoVs discussing their replication, pathogenicity, and current prevention and treatment strategies. We will also discuss the outbreaks of the highly pathogenic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV), which are relevant for understanding COVID-19.


Assuntos
Doenças dos Animais/virologia , Betacoronavirus/fisiologia , Galinhas/virologia , Infecções por Coronavirus/virologia , Coronavirus/fisiologia , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/virologia , Doenças dos Animais/diagnóstico , Doenças dos Animais/epidemiologia , Doenças dos Animais/prevenção & controle , Animais , Betacoronavirus/genética , Betacoronavirus/patogenicidade , Bovinos , Coronavirus/genética , Coronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Vírus da SARS/genética , Vírus da SARS/patogenicidade , Vírus da SARS/fisiologia , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Glicoproteína da Espícula de Coronavírus/genética , Suínos , Vírion , Replicação Viral
15.
Methods Mol Biol ; 2203: 167-184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833212

RESUMO

The Escherichia coli and vaccinia virus-based reverse genetics systems have been widely applied for the manipulation and engineering of coronavirus genomes. These systems, however, present several limitations and are sometimes difficult to establish in a timely manner for (re-)emerging viruses. In this chapter, we present a new universal reverse genetics platform for the assembly and engineering of infectious full-length cDNAs using yeast-based transformation-associated recombination cloning. This novel assembly method not only results in stable coronavirus infectious full-length cDNAs cloned in the yeast Saccharomyces cerevisiae but also fosters and accelerates the manipulation of their genomes. Such a platform is widely applicable for the scientific community, as it requires no specific equipment and can be performed in a standard laboratory setting. The protocol described can be easily adapted to virtually all known or emerging coronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV).


Assuntos
Coronavirus/genética , DNA Complementar/genética , Genômica/métodos , Saccharomyces cerevisiae/genética , Animais , Linhagem Celular , Coronavirus/patogenicidade , Recombinação Homóloga , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade
16.
Emerg Microbes Infect ; 9(1): 1965-1973, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32819220

RESUMO

Serology is a crucial part of the public health response to the ongoing SARS-CoV-2 pandemic. Here, we describe the development, validation and clinical evaluation of a protein micro-array as a quantitative multiplex immunoassay that can identify S and N-directed SARS-CoV-2 IgG antibodies with high specificity and sensitivity and distinguish them from all currently circulating human coronaviruses. The method specificity was 100% for SARS-CoV-2 S1 and 96% for N antigen based on extensive syndromic (n=230 cases) and population panel (n=94) testing that also confirmed the high prevalence of seasonal human coronaviruses. To assess its potential role for both SARS-CoV-2 patient diagnostics and population studies, we evaluated a large heterogeneous COVID-19 cohort (n=330) and found an overall sensitivity of 89% (≥ 21 days post onset symptoms (dps)), ranging from 86% to 96% depending on severity of disease. For a subset of these patients longitudinal samples were provided up to 56 dps. Mild cases showed absent or delayed, and lower SARS-CoV-2 antibody responses. Overall, we present the development and extensive clinical validation of a multiplex coronavirus serological assay for syndromic testing, to answer research questions regarding to antibody responses, to support SARS-CoV-2 diagnostics and to evaluate epidemiological developments efficiently and with high-throughput.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Proteínas do Nucleocapsídeo/sangue , Pneumonia Viral/diagnóstico , Glicoproteína da Espícula de Coronavírus/sangue , Idoso , Antígenos Virais/sangue , Antígenos Virais/imunologia , Betacoronavirus/patogenicidade , Técnicas de Laboratório Clínico/normas , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Testes de Neutralização , Proteínas do Nucleocapsídeo/imunologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Análise Serial de Proteínas , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia
17.
Respir Res ; 21(1): 224, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854739

RESUMO

Within two decades, there have emerged three highly pathogenic and deadly human coronaviruses, namely SARS-CoV, MERS-CoV and SARS-CoV-2. The economic burden and health threats caused by these coronaviruses are extremely dreadful and getting more serious as the increasing number of global infections and attributed deaths of SARS-CoV-2 and MERS-CoV. Unfortunately, specific medical countermeasures for these hCoVs remain absent. Moreover, the fast spread of misinformation about the ongoing SARS-CoV-2 pandemic uniquely places the virus alongside an annoying infodemic and causes unnecessary worldwide panic. SARS-CoV-2 shares many similarities with SARS-CoV and MERS-CoV, certainly, obvious differences exist as well. Lessons learnt from SARS-CoV and MERS-CoV, timely updated information of SARS-CoV-2 and MERS-CoV, and summarized specific knowledge of these hCoVs are extremely invaluable for effectively and efficiently contain the outbreak of SARS-CoV-2 and MERS-CoV. By gaining a deeper understanding of hCoVs and the illnesses caused by them, we can bridge knowledge gaps, provide cultural weapons for fighting and controling the spread of MERS-CoV and SARS-CoV-2, and prepare effective and robust defense lines against hCoVs that may emerge or reemerge in the future. To this end, the state-of-the-art knowledge and comparing the biological features of these lethal hCoVs and the clinical characteristics of illnesses caused by them are systematically summarized in the review.


Assuntos
Infecções por Coronavirus/epidemiologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/epidemiologia , Betacoronavirus , Controle de Doenças Transmissíveis , Feminino , Saúde Global , Humanos , Masculino , Prevalência , Medição de Risco , Análise de Sobrevida , Organização Mundial da Saúde
18.
Clin Microbiol Infect ; 26(10): 1436-1446, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32791241

RESUMO

BACKGROUND: There is currently no treatment known to alter the course of coronavirus disease 2019 (COVID-19). Convalescent plasma has been used to treat a number of infections during pandemics, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern respiratory syndrome coronavirus (MERS-CoV) and now severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). OBJECTIVES: To summarize the existing literature and registered clinical trials on the efficacy and safety of convalescent plasma for treating coronaviruses, and discuss issues of feasibility, and donor and patient selection. SOURCES: A review of articles published in PubMed was performed on 13 July 2020 to summarize the currently available evidence in human studies for convalescent plasma as a treatment for coronaviruses. The World Health Organization International Clinical Trials Registry and clinicaltrials.gov were searched to summarize the currently registered randomized clinical trials for convalescent plasma in COVID-19. CONTENT: There were sixteen COVID-19, four MERS and five SARS reports describing convalescent plasma use in humans. There were two randomized control trials, both of which were for COVID-19 and were terminated early. Most COVID-19 reports described a potential benefit of convalescent plasma on clinical outcomes in severe or critically ill patients with few immediate adverse events. However, there were a number of limitations, including the concurrent use of antivirals, steroids and other treatments, small sample sizes, lack of randomization or control groups, and short follow-up time. Data from SARS and COVID-19 suggest that earlier administration probably yields better outcomes. The ideal candidates for recipients and donors are not known. Still, experience with previous coronaviruses tells us that antibodies in convalescent patients are probably short-lived. Patients who had more severe disease and who are earlier in their course of recovery may be more likely to have adequate titres. Finally, a number of practical challenges were identified. IMPLICATIONS: There is currently no effective treatment for COVID-19, and preliminary trials for convalescent plasma suggest that there may be some benefits. However, research to date is at high risk of bias, and randomized control trials are desperately needed to determine the efficacy and safety of this therapeutic option.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/terapia , Antivirais/uso terapêutico , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Humanos , Imunização Passiva/métodos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Segurança do Paciente , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/mortalidade , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do Tratamento
19.
Immunol Rev ; 296(1): 205-219, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32658335

RESUMO

This article provides a review of studies evaluating the role of host (and viral) genetics (including variation in HLA genes) in the immune response to coronaviruses, as well as the clinical outcome of coronavirus-mediated disease. The initial sections focus on seasonal coronaviruses, SARS-CoV, and MERS-CoV. We then examine the state of the knowledge regarding genetic polymorphisms and SARS-CoV-2 and COVID-19. The article concludes by discussing research areas with current knowledge gaps and proposes several avenues for future scientific exploration in order to develop new insights into the immunology of SARS-CoV-2.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Resistência à Doença/genética , Predisposição Genética para Doença , Interações Hospedeiro-Patógeno/genética , Pneumonia Viral/imunologia , Animais , Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/genética , Pneumonia Viral/virologia , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/virologia
20.
Trends Biotechnol ; 38(9): 943-947, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32600777

RESUMO

Vaccine solutions rarely reach the public until after an outbreak abates; an Ebola vaccine was approved 5 years after peak outbreak and SARS, MERS, and Zika vaccines are still in clinical development. Despite massive leaps forward in rapid science, other regulatory bottlenecks are hamstringing the global effort for pandemic vaccines.


Assuntos
Infecções por Coronavirus/prevenção & controle , Aprovação de Drogas/organização & administração , Doença pelo Vírus Ebola/prevenção & controle , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/biossíntese , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Vacinas contra Ebola/administração & dosagem , Vacinas contra Ebola/biossíntese , Ebolavirus/efeitos dos fármacos , Ebolavirus/imunologia , Ebolavirus/patogenicidade , Europa (Continente)/epidemiologia , Saúde Global/tendências , Regulamentação Governamental , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/biossíntese , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Humana/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Síndrome Respiratória Aguda Grave/virologia , Estados Unidos/epidemiologia , Vacinas Virais/administração & dosagem , Zika virus/efeitos dos fármacos , Zika virus/imunologia , Zika virus/patogenicidade , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/imunologia , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/virologia
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