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1.
Adv Exp Med Biol ; 1318: 23-39, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33973170

RESUMO

The ongoing coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is highly contagious and fatal, posing a direct threat to human health and the global economy. Most strategies to prevent, control, and eradicate COVID-19 are established based on the specific characteristics of the pathogen. The quest for interruption and eradication of COVID-19 has moved research forward in understanding fundamental aspects of the virus genome, proteome, replication mechanisms, and virus-host interactions, which pave the way for the development of effective antiviral drugs and vaccines. This chapter provides an overview of recent progress in human coronavirus taxonomy, molecular features of the SARS-CoV-2 genome and proteome, and virus life cycle.


Assuntos
Coronavirus , Antivirais/uso terapêutico , Classificação , Coronavirus/genética , Coronavirus/patogenicidade , Genoma Viral/genética , Humanos
2.
Biomolecules ; 11(5)2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946644

RESUMO

Severely ill coronavirus disease 2019 (COVID-19) patients show elevated concentrations of pro-inflammatory cytokines, a situation commonly known as a cytokine storm. The p38 MAPK receptor is considered a plausible therapeutic target because of its involvement in the platelet activation processes leading to inflammation. This study aimed to identify potential natural product-derived inhibitory molecules against the p38α MAPK receptor to mitigate the eliciting of pro-inflammatory cytokines using computational techniques. The 3D X-ray structure of the receptor with PDB ID 3ZS5 was energy minimized using GROMACS and used for molecular docking via AutoDock Vina. The molecular docking was validated with an acceptable area under the curve (AUC) of 0.704, which was computed from the receiver operating characteristic (ROC) curve. A compendium of 38,271 natural products originating from Africa and China together with eleven known p38 MAPK inhibitors were screened against the receptor. Four potential lead compounds ZINC1691180, ZINC5519433, ZINC4520996 and ZINC5733756 were identified. The compounds formed strong intermolecular bonds with critical residues Val38, Ala51, Lys53, Thr106, Leu108, Met109 and Phe169. Additionally, they exhibited appreciably low binding energies which were corroborated via molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations. The compounds were also predicted to have plausible pharmacological profiles with insignificant toxicity. The molecules were also predicted to be anti-inflammatory, kinase inhibitors, antiviral, platelet aggregation inhibitors, and immunosuppressive, with probable activity (Pa) greater than probable inactivity (Pi). ZINC5733756 is structurally similar to estradiol with a Tanimoto coefficient value of 0.73, which exhibits anti-inflammatory activity by targeting the activation of Nrf2. Similarly, ZINC1691180 has been reported to elicit anti-inflammatory activity in vitro. The compounds may serve as scaffolds for the design of potential biotherapeutic molecules against the cytokine storm associated with COVID-19.


Assuntos
/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Produtos Biológicos/metabolismo , Coronavirus/patogenicidade , Citocinas/metabolismo , Humanos , Inflamação/metabolismo , Simulação de Acoplamento Molecular , Curva ROC
3.
Indian J Tuberc ; 68(1): 92-98, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33641858

RESUMO

In December 2019, a large number of coronavirus cases were emerged in Wuhan, Hubei Province, China and rapidly spread to different countries and territories around the world within four months. The World Health Organization (WHO) declared this outbreak as a global health emergency. The spread of COVID-19 over globe is highly contagious; they transmitted from person-to-person through small droplets of infected person. Many diagnosis and treatment methods have been implemented to reduce and control the outbreak. Efforts have been made to develop coronavirus vaccine against S protein or spike glycoprotein of coronavirus. COVID-19 outbreak will affect the Gross Domestic Product (GDP) of the world. At the time of preparing manuscript, total number of active cases reaches to more than 8.9 million and confirmed death reaches to approx. 4.6 lakh. This article highlights the ongoing research and advances in designing vaccine and therapeutics against COVID-19 and also focusing on the epidemiology, transmission, future direction and control the spread of infectious diseases.


Assuntos
/epidemiologia , /terapia , /diagnóstico , Controle de Doenças Transmissíveis , Coronavirus/patogenicidade , Produto Interno Bruto , Humanos , Imunização Passiva , Controle de Infecções , Pandemias , /patogenicidade
4.
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 , /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 , Especificidade da Espécie , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Transcrição Genética/efeitos dos fármacos , Transcrição Genética/genética
5.
mBio ; 12(2)2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653891

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the CoV disease 2019 (COVID-19) pandemic, enters host cells via the interaction of its receptor-binding domain (RBD) of the spike protein with host angiotensin-converting enzyme 2 (ACE2). Therefore, the RBD is a promising vaccine target to induce protective immunity against SARS-CoV-2 infection. In this study, we report the development of an RBD protein-based vaccine candidate against SARS-CoV-2 using self-assembling Helicobacter pylori-bullfrog ferritin nanoparticles as an antigen delivery system. RBD-ferritin protein purified from mammalian cells efficiently assembled into 24-mer nanoparticles. Sixteen- to 20-month-old ferrets were vaccinated with RBD-ferritin nanoparticles (RBD nanoparticles) by intramuscular or intranasal inoculation. All vaccinated ferrets with RBD nanoparticles produced potent neutralizing antibodies against SARS-CoV-2. Strikingly, vaccinated ferrets demonstrated efficient protection from SARS-CoV-2 challenge, showing no fever, body weight loss, or clinical symptoms. Furthermore, vaccinated ferrets showed rapid clearance of infectious virus in nasal washes and lungs as well as of viral RNA in respiratory organs. This study demonstrates that spike RBD-nanoparticles are an effective protein vaccine candidate against SARS-CoV-2.


Assuntos
/prevenção & controle , Nanopartículas/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas Virais/uso terapêutico , /química , Animais , Celulose/química , Coronavirus/imunologia , Coronavirus/patogenicidade , Furões , Ferritinas , Vacinas Virais/química
6.
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 , /transmissão , Quirópteros/virologia , Coronavirus/classificação , Coronavirus/genética , Coronavirus/patogenicidade , Especificidade de Hospedeiro , Humanos , /genética , Zoonoses/prevenção & controle , Zoonoses/virologia
7.
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
/transmissão , Gatos/virologia , Animais , /virologia , Coronavirus/classificação , Coronavirus/isolamento & purificação , Coronavirus/patogenicidade , Especificidade de Hospedeiro , Humanos , Vison/virologia , Prevalência , /isolamento & purificação , Zoonoses/epidemiologia , Zoonoses/prevenção & controle , Zoonoses/virologia
8.
Vet Pathol ; 58(3): 438-452, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33357102

RESUMO

Coronaviruses (CoVs) comprise a large group of positive stranded RNA viruses that infect a diverse host range including birds and mammals. Infection with CoVs typically presents as mild to severe respiratory or enteric disease, but CoVs have the potential to cause significant morbidity or mortality in highly susceptible age groups. CoVs have exhibited a penchant for jumping species barriers throughout history with devastating effects. The emergence of highly pathogenic or infectious CoVs in humans over the past 20 years, including severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and most recently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underscores the significant threat that CoV spillovers pose to humans. Similar to the emergence of SARS-CoV-2, CoVs have been devastating to commercial animal production over the past century, including infectious bronchitis virus in poultry and bovine CoV, as well as the emergence and reemergence of multiple CoVs in swine including transmissible gastroenteritis virus, porcine epidemic diarrhea virus, and porcine deltacoronavirus. These naturally occurring animal CoV infections provide important examples for understanding CoV disease as many animal CoVs have complex pathogenesis similar to SARS-CoV-2 and can shed light on the ongoing SARS-CoV-2 outbreak. We provide an overview and update regarding selected existing animal CoVs and their primary host species, diseases caused by CoVs, how CoVs jump species, whether these CoVs pose an outbreak risk or risk to humans, and how we can mitigate these risks.


Assuntos
Infecções por Coronavirus/virologia , Coronavirus/fisiologia , Animais , Aves , Coronavirus/classificação , Coronavirus/patogenicidade , Infecções por Coronavirus/transmissão , Modelos Animais de Doenças , Humanos , Mamíferos , Filogenia
9.
PLoS One ; 15(12): e0244052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33320910

RESUMO

INTRODUCTION: The novel Coronavirus Disease (COVID-19) outbreak currently puts health care workers at high risk of both physical and mental health problems. This study aimed to identify the risk and protective factors for mental health outcomes in health care workers during coronavirus epidemics. METHODS: A rapid systematic review was performed in three databases (March 24, 2020) and a current COVID-19 resource (May 28, 2020). Following study selection, study characteristics and effect measures were tabulated, and data were synthesized by using vote counting. Meta-analysis was not possible because of high variation in risk factors, outcomes and effect measures. Risk of bias of each study was assessed and the certainty of evidence was appraised according to the GRADE methodology. RESULTS: Out of 2605 references, 33 observational studies were selected and the identified risk and protective factors were categorized in ten thematic categories. Most of these studies (n = 23) were performed during the SARS outbreak, seven during the current COVID-19 pandemic and three during the MERS outbreak. The level of disease exposure and health fear were significantly associated with worse mental health outcomes. There was evidence that clear communication and support from the organization, social support and personal sense of control are protective factors. The evidence was of very low certainty, because of risk of bias and imprecision. CONCLUSION: Safeguarding mental health of health care workers during infectious disease outbreaks should not be treated as a separate mental health intervention strategy, but could benefit from a protective approach. This study suggests that embedding mental health support in a safe and efficient working environment which promotes collegial social support and personal sense of control could help to maximize resilience of health care workers. Low quality cross-sectional studies currently provide the best possible evidence, and further research is warranted to confirm causality.


Assuntos
/epidemiologia , Infecções por Coronavirus/epidemiologia , Saúde Mental , Síndrome Respiratória Aguda Grave/epidemiologia , /complicações , Coronavirus/patogenicidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Estudos Transversais , Surtos de Doenças , Pessoal de Saúde , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/virologia
10.
Med Sci Monit ; 26: e928835, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33335084

RESUMO

BACKGROUND This study summarizes the characteristics of children screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reports the case of 1 child who was diagnosed with SARS-CoV-2 infection in Guangzhou Women and Children's Medical Center and the cases of his family members. MATERIAL AND METHODS The medical records of 159 children who were admitted to our hospital from January 23 to March 20, 2020, were retrospectively analyzed. Samples from pharyngeal or/and anal swabs were subjected to reverse-transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 within 12 h of patient admission; a second RT-PCR test was done 24 h after the first test. RESULTS Of the 159 patients, 151 patients had epidemiological histories, 14 patients had cluster onset, and 8 patients had no epidemiological history but had symptoms similar to coronavirus disease 2019 (COVID-19). The most common symptom was fever (n=125), followed by respiratory and gastrointestinal symptoms. A 7-year-old boy in a cluster family from Wuhan was confirmed with asymptomatic SARS-CoV-2 infection with ground-glass opacity shadows on his lung computed tomography scan, and his swab RT-PCR test had not turned negative until day 19 of his hospitalization. In patients who did not test positive for SARS-CoV-2, influenza, respiratory syncytial virus, and adenovirus were observed. A total of 158 patients recovered, were discharged, and experienced no abnormalities during follow-up. CONCLUSIONS For SARS-CoV-2 nosocomial infections, taking a "standard prevention & contact isolation & droplet isolation & air isolation" strategy can prevent infection effectively. Children with clustered disease need close monitoring.


Assuntos
/diagnóstico , /epidemiologia , /métodos , Criança , Pré-Escolar , China/epidemiologia , Coronavirus/metabolismo , Coronavirus/patogenicidade , Infecção Hospitalar/epidemiologia , Feminino , Febre , Hospitalização , Hospitais , Humanos , Masculino , Registros Médicos , Alta do Paciente , Estudos Retrospectivos , /patogenicidade
11.
Med Sci Monit ; 26: e928849, 2020 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-33339813

RESUMO

BACKGROUND Emerging studies noted that liver injury in coronavirus disease 2019 (COVID-19) patients may be induced by virus-mediated inflammation, which was confirmed by liver pathology. The aim of this study was to observe clinical characteristics and explore risk factors in COVID-19 patients with liver injury. MATERIAL AND METHODS In this retrospective study, 40 confirmed COVID-19 patients with normal alanine transaminase (ALT) on admission were divided into a group of normal ALT patients whose ALT was always less than 40 U/l during hospitalization and a group of elevated ALT patients whose ALT was at least once more than 40 U/l after admission. Clinical data, especially virus-induced inflammatory parameters, were analyzed for risk factors and predictive value. The Mann-Whitney U test and t test for comparing means and logistic regression were performed for analysis of risk factors. Area under the ROC curve was used for predictive values. RESULTS Sixteen of 40 (40.0%) patients developed elevated ALT, many of them with more severe COVID-19. The highest ALT level was 101 U/l. The risk factors for liver injury were C-reactive protein (CRP), interleukin 6 (IL6), erythrocyte sedimentation rate (ESR), CD8+T cell count, and severity of disease, and CRP (OR 1.13, 95% CI 1.045-1.222, p=0.002) was the independent risk factor. CONCLUSIONS Liver injury in COVID-19 patients was mild and associated with inflammatory markers, especially CRP, which suggests that liver injury may be induced by virus-mediated inflammation in COVID-19 patients.


Assuntos
/epidemiologia , Fígado/metabolismo , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores , Sedimentação Sanguínea , Proteína C-Reativa/análise , China/epidemiologia , Coronavirus/patogenicidade , Feminino , Hospitalização , Humanos , Interleucina-6/análise , Fígado/lesões , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , /patogenicidade
12.
Med Sci Monit ; 26: e927674, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33342993

RESUMO

BACKGROUND The aim of this study was to analyze the clinical features and laboratory indices of patients with coronavirus disease (COVID-19) and explore their association with the severity of the disease. MATERIAL AND METHODS A total of 61 patients with COVID-19 were divided into groups with common symptoms and with severe diseases, and clinical data were collected to analyze and compare the differences between them. RESULTS In patients with severe COVID-19, compared with the common group, lymphocyte count and albumin levels were lower, and aspartate aminotransferase (AST), blood urea, blood creatinine, lactate dehydrogenase (LDH), and C-reactive protein (CRP) levels, and prothrombin time (PT) were elevated (all P<0.05). The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume-to-lymphocyte ratio (MPVLR), and C-reactive protein-to-albumin ratio (CAR) were significantly elevated in the severe group compared with the group with common symptoms; however, the lymphocyte-to-monocyte ratio (LMR) was significantly reduced (P<0.05). Univariate logistic regression showed that lower lymphocyte count, prolonged PT, elevated CRP and LDH levels, and elevated NLR, PLR, MPVLR, and CAR were risk factors for COVID-19 severity (P<0.05). Multivariate logistic regression showed that elevated CRP levels (odds ratio [OR], 0.028; 95% confidence interval [CI]: 0.002-0.526; P=0.017), prolonged PT (OR, 0.014; 95% CI: 0.001-0.341; P=0.09), and an MPVLR >8.9 (OR, 0.026; 95% CI: 0.002-0.349; P=0.006) were independent risk factors for COVID-19 severity. CONCLUSIONS Elevated CRP and prolonged PT, and an MPVLR >8.9 were independent risk factors for COVID-19 severity.


Assuntos
/epidemiologia , Infecções por Coronavirus/diagnóstico , Adulto , Aspartato Aminotransferases/sangue , Plaquetas , Proteína C-Reativa/análise , China/epidemiologia , Coronavirus/patogenicidade , Infecções por Coronavirus/sangue , Creatinina/análise , Feminino , Humanos , Pacientes Internados , L-Lactato Desidrogenase/sangue , Contagem de Linfócitos , Linfócitos/química , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Monócitos , Neutrófilos/química , Estudos Retrospectivos , Albumina Sérica/análise , Índice de Gravidade de Doença
13.
PLoS One ; 15(12): e0244518, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33370781

RESUMO

Spread of pathogens on contaminated surfaces plays a key role in disease transmission. Surface technologies that control pathogen transfer can help control fomite transmission and are of great interest to public health. Here, we report a novel bead transfer method for evaluating fomite transmission in common laboratory settings. We show that this method meets several important criteria for quantitative test methods, including reasonableness, relevancy, resemblance, responsiveness, and repeatability, and therefore may be adaptable for standardization. In addition, this method can be applied to a wide variety of pathogens including bacteria, phage, and human viruses. Using the bead transfer method, we demonstrate that an engineered micropattern limits transfer of Staphylococcus aureus by 97.8% and T4 bacteriophage by 93.0% on silicone surfaces. Furthermore, the micropattern significantly reduces transfer of influenza B virus and human coronavirus on silicone and polypropylene surfaces. Our results highlight the potential of using surface texture as a valuable new strategy in combating infectious diseases.


Assuntos
Bacteriófago T4/patogenicidade , Bacteriófagos/patogenicidade , Coronavirus/patogenicidade , Vírus da Influenza B/patogenicidade , Infecções Estafilocócicas/terapia , Staphylococcus aureus/patogenicidade , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Fômites/microbiologia , Fômites/virologia , Humanos , Influenza Humana/transmissão , Influenza Humana/virologia , Silicones
14.
PLoS One ; 15(12): e0243735, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315873

RESUMO

INTRODUCTION: Wheezing is a major problem in children, and respiratory viruses are often believed to be the causative agent. While molecular detection tools enable identification of respiratory viruses in wheezing children, it remains unclear if and how these viruses are associated with wheezing. The objective of this systematic review is to clarify the prevalence of different respiratory viruses in children with wheezing. METHODS: We performed an electronic in Pubmed and Global Index Medicus on 01 July 2019 and manual search. We performed search of studies that have detected common respiratory viruses in children ≤18 years with wheezing. We included only studies using polymerase chain reaction (PCR) assays. Study data were extracted and the quality of articles assessed. We conducted sensitivity, subgroup, publication bias, and heterogeneity analyses using a random effects model. RESULTS: The systematic review included 33 studies. Rhinovirus, with a prevalence of 35.6% (95% CI 24.6-47.3, I2 98.4%), and respiratory syncytial virus, at 31.0% (95% CI 19.9-43.3, I2 96.4%), were the most common viruses detected. The prevalence of other respiratory viruses was as follows: human bocavirus 8.1% (95% CI 5.3-11.3, I2 84.6%), human adenovirus 7.7% (95% CI 2.6-15.0, I2 91.0%), influenza virus6.5% (95% CI 2.2-12.6, I2 92.4%), human metapneumovirus5.8% (95% CI 3.4-8.8, I2 89.0%), enterovirus 4.3% (95% CI 0.1-12.9, I2 96.2%), human parainfluenza virus 3.8% (95% CI 1.5-6.9, I2 79.1%), and human coronavirus 2.2% (95% CI 0.6-4.4, I2 79.4%). CONCLUSIONS: Our results suggest that rhinovirus and respiratory syncytial virus may contribute to the etiology of wheezing in children. While the clinical implications of molecular detection of respiratory viruses remains an interesting question, this study helps to illuminate the potential of role respiratory viruses in pediatric wheezing. REVIEW REGISTRATION: PROSPERO, CRD42018115128.


Assuntos
Sons Respiratórios/etiologia , Sons Respiratórios/genética , Infecções Respiratórias/diagnóstico , Bocavirus/genética , Bocavirus/isolamento & purificação , Bocavirus/patogenicidade , Criança , Pré-Escolar , Coronavirus/isolamento & purificação , Coronavirus/patogenicidade , Humanos , Orthomyxoviridae/genética , Orthomyxoviridae/isolamento & purificação , Orthomyxoviridae/patogenicidade , Vírus da Parainfluenza 1 Humana/genética , Vírus da Parainfluenza 1 Humana/isolamento & purificação , Vírus da Parainfluenza 1 Humana/patogenicidade , Reação em Cadeia da Polimerase , Sons Respiratórios/fisiopatologia , Sistema Respiratório/patologia , Sistema Respiratório/virologia , Infecções Respiratórias/genética , Infecções Respiratórias/virologia
15.
Viruses ; 12(12)2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33316899

RESUMO

Emerging infectious diseases are of great concern to public health, as highlighted by the ongoing coronavirus disease 2019 (COVID-19) pandemic. Such diseases are of particular danger during mass gathering and mass influx events, as large crowds of people in close proximity to each other creates optimal opportunities for disease transmission. The Hashemite Kingdom of Jordan and the Kingdom of Saudi Arabia are two countries that have witnessed mass gatherings due to the arrival of Syrian refugees and the annual Hajj season. The mass migration of people not only brings exotic diseases to these regions but also brings new diseases back to their own countries, e.g., the outbreak of MERS in South Korea. Many emerging pathogens originate in bats, and more than 30 bat species have been identified in these two countries. Some of those bat species are known to carry viruses that cause deadly diseases in other parts of the world, such as the rabies virus and coronaviruses. However, little is known about bats and the pathogens they carry in Jordan and Saudi Arabia. Here, the importance of enhanced surveillance of bat-borne infections in Jordan and Saudi Arabia is emphasized, promoting the awareness of bat-borne diseases among the general public and building up infrastructure and capability to fill the gaps in public health preparedness to prevent future pandemics.


Assuntos
Quirópteros/virologia , Doenças Transmissíveis Emergentes/epidemiologia , Coronavirus/isolamento & purificação , Saúde Pública , Zoonoses/epidemiologia , Animais , Doenças Transmissíveis Emergentes/virologia , Coronavirus/classificação , Coronavirus/patogenicidade , Surtos de Doenças/prevenção & controle , Humanos , Jordânia , Arábia Saudita , Zoonoses/transmissão , Zoonoses/virologia
16.
PLoS One ; 15(12): e0244025, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33351847

RESUMO

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


Assuntos
/genética , Coronavirus/genética , Citidina Desaminase/genética , Proteínas de Ligação a RNA/genética , Proteínas Repressoras/genética , Animais , /virologia , Bovinos , Coronavirus/classificação , Coronavirus/patogenicidade , Cães , Evolução Molecular , Genoma Viral/genética , Humanos , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Vírus da SARS/genética , Vírus da SARS/patogenicidade , /patogenicidade , Suínos/virologia
17.
Viruses ; 12(10)2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33096825

RESUMO

Most cells can release extracellular vesicles (EVs), membrane vesicles containing various proteins, nucleic acids, enzymes, and signaling molecules. The exchange of EVs between cells facilitates intercellular communication, amplification of cellular responses, immune response modulation, and perhaps alterations in viral pathogenicity. EVs serve a dual role in inhibiting or enhancing viral infection and pathogenesis. This review examines the current literature on EVs to explore the complex role of EVs in the enhancement, inhibition, and potential use as a nanotherapeutic against clinically relevant viruses, focusing on neurotropic viruses: Zika virus (ZIKV) and human immunodeficiency virus (HIV). Overall, this review's scope will elaborate on EV-based mechanisms, which impact viral pathogenicity, facilitate viral spread, and modulate antiviral immune responses.


Assuntos
Vesículas Extracelulares/metabolismo , Viroses/metabolismo , Antivirais/farmacologia , Comunicação Celular/fisiologia , Coronavirus/metabolismo , Coronavirus/patogenicidade , Exossomos/metabolismo , HIV/metabolismo , HIV/patogenicidade , Infecções por HIV/metabolismo , Humanos , Retroviridae/metabolismo , Simplexvirus/metabolismo , Terapêutica/métodos , Viroses/tratamento farmacológico , Viroses/virologia , Zika virus/metabolismo , Zika virus/patogenicidade , Infecção por Zika virus/metabolismo
18.
Euro Surveill ; 25(40)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33034281

RESUMO

BackgroundThe natural history of disease in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remained obscure during the early pandemic.AimOur objective was to estimate epidemiological parameters of coronavirus disease (COVID-19) and assess the relative infectivity of the incubation period.MethodsWe estimated the distributions of four epidemiological parameters of SARS-CoV-2 transmission using a large database of COVID-19 cases and potential transmission pairs of cases, and assessed their heterogeneity by demographics, epidemic phase and geographical region. We further calculated the time of peak infectivity and quantified the proportion of secondary infections during the incubation period.ResultsThe median incubation period was 7.2 (95% confidence interval (CI): 6.9‒7.5) days. The median serial and generation intervals were similar, 4.7 (95% CI: 4.2‒5.3) and 4.6 (95% CI: 4.2‒5.1) days, respectively. Paediatric cases < 18 years had a longer incubation period than adult age groups (p = 0.007). The median incubation period increased from 4.4 days before 25 January to 11.5 days after 31 January (p < 0.001), whereas the median serial (generation) interval contracted from 5.9 (4.8) days before 25 January to 3.4 (3.7) days after. The median time from symptom onset to discharge was also shortened from 18.3 before 22 January to 14.1 days after. Peak infectivity occurred 1 day before symptom onset on average, and the incubation period accounted for 70% of transmission.ConclusionThe high infectivity during the incubation period led to short generation and serial intervals, necessitating aggressive control measures such as early case finding and quarantine of close contacts.


Assuntos
Infecções por Coronavirus/transmissão , Coronavirus/patogenicidade , Período de Incubação de Doenças Infecciosas , Pneumonia Viral/transmissão , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Criança , Pré-Escolar , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Estudos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Adulto Jovem
19.
Electromagn Biol Med ; 39(4): 433-436, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33016156

RESUMO

To help investigate the relationship between inflammatory and other symptoms of coronavirus and the protein-protein interactions (PPI) that occur between viral proteins and protein molecules of the host cell, I propose that the electrostatic discharge (ESD) exists including corona discharge to lead to ozone gas. I cite evidence in support of this hypothesis. I hope that the proposed will inspire new studies in finding effective treatments and vaccines for individuals with coronavirus disease in 2019. I suggest possible future studies that may lend more credibility to the proposed.


Assuntos
Betacoronavirus/fisiologia , Coronavirus/fisiologia , Modelos Biológicos , Eletricidade Estática , Betacoronavirus/química , Betacoronavirus/patogenicidade , Coronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Sistema de Condução Cardíaco/efeitos dos fármacos , Sistema de Condução Cardíaco/fisiopatologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Hidroxicloroquina/farmacologia , Ozônio/metabolismo , Ozônio/toxicidade , Perda de Ozônio , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Domínios e Motivos de Interação entre Proteínas/fisiologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/fisiologia
20.
Clin Lab Med ; 40(4): 459-472, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33121615

RESUMO

Endemic species of coronavirus (HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1) are frequent causes of upper respiratory tract infections. Three highly pathogenic coronaviruses have been associated with outbreaks and epidemics and have challenged clinical microbiology laboratories to quickly develop assays for diagnosis. Their initial characterization was achieved by molecular methods. With the great advance in metagenomic whole-genome sequencing directly from clinical specimens, diagnosis of novel coronaviruses could be quickly implemented into the workflow of managing cases of pneumonia of unknown cause, which will markedly affect the time of the initial characterization and accelerate the initiation of outbreak control measures.


Assuntos
Controle de Doenças Transmissíveis/métodos , Coronavirus , Surtos de Doenças/prevenção & controle , Técnicas Microbiológicas/métodos , Infecções Respiratórias , Serviços de Laboratório Clínico , Coronavirus/classificação , Coronavirus/genética , Coronavirus/isolamento & purificação , Coronavirus/patogenicidade , Humanos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Sequenciamento Completo do Genoma
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