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1.
Biomedica ; 40(Supl. 2): 148-158, 2020 10 30.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33152198

RESUMO

Introduction: SARS-CoV-2 has been identified as the new coronavirus causing an outbreak of acute respiratory disease in China in December, 2019. This disease, currently named COVID-19, has been declared as a pandemic by the World Health Organization (WHO). The first case of COVID-19 in Colombia was reported on March 6, 2020. Here we characterize an early SARS-CoV-2 isolate from the pandemic recovered in April, 2020. Objective: To describe the isolation and characterization of an early SARS-CoV-2 isolate from the epidemic in Colombia. Materials and methods: A nasopharyngeal specimen from a COVID-19 positive patient was inoculated on different cell lines. To confirm the presence of SARS-CoV-2 on cultures we used qRT-PCR, indirect immunofluorescence assay, transmission and scanning electron microscopy, and next-generation sequencing. Results: We determined the isolation of SARS-CoV-2 in Vero-E6 cells by the appearance of the cytopathic effect three days post-infection and confirmed it by the positive results in the qRT-PCR and the immunofluorescence with convalescent serum. Transmission and scanning electron microscopy images obtained from infected cells showed the presence of structures compatible with SARS-CoV-2. Finally, a complete genome sequence obtained by next-generation sequencing allowed classifying the isolate as B.1.5 lineage. Conclusion: The evidence presented in this article confirms the first isolation of SARSCoV-2 in Colombia. In addition, it shows that this strain behaves in cell culture in a similar way to that reported in the literature for other isolates and that its genetic composition is consistent with the predominant variant in the world. Finally, points out the importance of viral isolation for the detection of neutralizing antibodies, for the genotypic and phenotypic characterization of the strain and for testing compounds with antiviral potential.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Pandemias , Pneumonia Viral/virologia , RNA Viral/genética , Animais , Betacoronavirus/genética , Betacoronavirus/fisiologia , Betacoronavirus/ultraestrutura , Chlorocebus aethiops , Colômbia/epidemiologia , Convalescença , Infecções por Coronavirus/epidemiologia , Efeito Citopatogênico Viral , Técnica Indireta de Fluorescência para Anticorpo , Genoma Viral , Humanos , Microscopia Eletrônica , Tipagem Molecular , Nasofaringe/virologia , Pneumonia Viral/epidemiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de RNA , Especificidade da Espécie , Células Vero , Vírion/ultraestrutura , Cultura de Vírus
2.
Niger J Physiol Sci ; 35(1): 20-25, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33084624

RESUMO

Severe Acute Respiratory human Coronavirus 2 (SARS-hCOV 2) infection which began in December 2019 has rapidly disseminated worldwide due to non-availability of anti-viral treatment or vaccine, no knowledge of virus-human interaction, lack of prognostic factors for stages of illness and ability of hCoV 2 to rapidly mutate and infect multiple cell types. Host inflammation and evasion of host immune responses by viruses are believed to play major roles in disease severity of human Corona viruses (hCoVs), thus uses of anti-inflammatory and immune-boosting agents apart from complete multi-disciplinary approach are suggested to combat the ranvaging SAR-hCOV 2 infection. This paper related the structural proteins and life cycle of CoV with host immune responses to CoV. This is to bring out gaps in knowledge for possible future researches.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Interações Hospedeiro-Patógeno/imunologia , Pneumonia Viral/imunologia , Betacoronavirus/ultraestrutura , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/virologia , Proteínas Estruturais Virais/fisiologia
3.
Sci Rep ; 10(1): 16099, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999356

RESUMO

SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Here, we investigated the interaction of this new coronavirus with Vero cells using high resolution scanning electron microscopy. Surface morphology, the interior of infected cells and the distribution of viral particles in both environments were observed 2 and 48 h after infection. We showed areas of viral processing, details of vacuole contents, and viral interactions with the cell surface. Intercellular connections were also approached, and viral particles were adhered to these extensions suggesting direct cell-to-cell transmission of SARS-CoV-2.


Assuntos
Betacoronavirus/ultraestrutura , Infecções por Coronavirus/transmissão , Interações Hospedeiro-Patógeno/fisiologia , Pneumonia Viral/transmissão , Animais , Linhagem Celular , Chlorocebus aethiops , Infecções por Coronavirus/patologia , Humanos , Microscopia Eletrônica de Varredura , Pandemias , Pneumonia Viral/patologia , Células Vero
4.
Structure ; 28(11): 1218-1224.e4, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33058760

RESUMO

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) resulted from the outbreak of SARS-CoV-2 in December 2019. Currently, multiple efforts are being made to rapidly develop vaccines and treatments to fight COVID-19. Current vaccine candidates use inactivated SARS-CoV-2 viruses; therefore, it is important to understand the architecture of inactivated SARS-CoV-2. We have genetically and structurally characterized ß-propiolactone-inactivated viruses from a propagated and purified clinical strain of SARS-CoV-2. We observed that the virus particles are roughly spherical or moderately pleiomorphic. Although a small fraction of prefusion spikes are found, most spikes appear nail shaped, thus resembling a postfusion state, where the S1 protein of the spike has disassociated from S2. Cryoelectron tomography and subtomogram averaging of these spikes yielded a density map that closely matches the overall structure of the SARS-CoV postfusion spike and its corresponding glycosylation site. Our findings have major implications for SARS-CoV-2 vaccine design, especially those using inactivated viruses.


Assuntos
Betacoronavirus/ultraestrutura , Desinfetantes/farmacologia , Propiolactona/farmacologia , Vírion/efeitos dos fármacos , Animais , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Chlorocebus aethiops , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Microscopia Crioeletrônica , Tomografia com Microscopia Eletrônica , Humanos , Glicoproteína da Espícula de Coronavírus/ultraestrutura , Vacinas de Produtos Inativados/imunologia , Células Vero , Vacinas Virais/imunologia , Vírion/ultraestrutura
5.
Niger J Physiol Sci ; 35(1): 10-19, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-33084621

RESUMO

Coronavirus Disease 2019 is a wide-spreading severe viral disease caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) virus that needs to be urgently eradicated. SARS-COV-2 has infected millions of people worldwide and results in more than three hundred thousand deaths. Several repurposed drugs have failed to successfully eradicate the infection. Multiorgan failure caused by pronounced inflammation and systemic coagulation accounts for severe complications and death associated with diseases. Bromelain appears to be a potential candidate that may be used to inhibit or prevent the symptoms of the diseases. Its anti-inflammatory and anticoagulatory properties make it a potential agent that may slow the progression of the disease. In this review, we highlighted the beneficial effects of bromelain based on both experimental and clinical evidence that make bromelain a good candidate for the treatment of symptoms of CoVID-19 infection.


Assuntos
Bromelaínas/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Fitoterapia , Pneumonia Viral/tratamento farmacológico , Ananas , Betacoronavirus/ultraestrutura , Bromelaínas/farmacologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia
7.
Adv Healthc Mater ; 9(19): e2000979, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32885616

RESUMO

Researchers, engineers, and medical doctors are made aware of the severity of the COVID-19 infection and act quickly against the coronavirus SARS-CoV-2 using a large variety of tools. In this review, a panoply of nanoscience and nanotechnology approaches show how these disciplines can help the medical, technical, and scientific communities to fight the pandemic, highlighting the development of nanomaterials for detection, sanitation, therapies, and vaccines. SARS-CoV-2, which can be regarded as a functional core-shell nanoparticle (NP), can interact with diverse materials in its vicinity and remains attached for variable times while preserving its bioactivity. These studies are critical for the appropriate use of controlled disinfection systems. Other nanotechnological approaches are also decisive for the development of improved novel testing and diagnosis kits of coronavirus that are urgently required. Therapeutics are based on nanotechnology strategies as well and focus on antiviral drug design and on new nanoarchitectured vaccines. A brief overview on patented work is presented that emphasizes nanotechnology applied to coronaviruses. Finally, some comments are made on patents of the initial technological responses to COVID-19 that have already been put in practice.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nanotecnologia/métodos , Pandemias , Pneumonia Viral , Antivirais/administração & dosagem , Betacoronavirus/química , Betacoronavirus/ultraestrutura , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Desinfecção/métodos , Humanos , Nanopartículas/química , Nanopartículas/ultraestrutura , Nanoestruturas/química , Nanotecnologia/legislação & jurisprudência , Pandemias/prevenção & controle , Patentes como Assunto , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Propriedades de Superfície , Vacinas Virais/administração & dosagem
8.
Nano Lett ; 20(10): 7642-7647, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-32986441

RESUMO

Shortages in the availability of personal protective face masks during the COVID-19 pandemic required many to fabricate masks and filter inserts from available materials. While the base filtration efficiency of a material is of primary importance when a perfect seal is possible, ideal fit is not likely to be achieved by the average person preparing to enter a public space or even a healthcare worker without fit-testing before each shift. Our findings suggest that parameters including permeability and pliability can play a strong role in the filtration efficiency of a mask fabricated with various filter media, and that the filtration efficiency of loosely fitting masks/respirators against ultrafine particulates can drop by more than 60% when worn compared to the ideal filtration efficiency of the base material. Further, a test method using SARS-CoV-2 virion-sized silica nanoaerosols is demonstrated to assess the filtration efficiency against nanoparticulates that follow air currents associated with mask leakage.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Filtração/instrumentação , Máscaras , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Dispositivos de Proteção Respiratória , Têxteis , Aerossóis , Microbiologia do Ar , Betacoronavirus/ultraestrutura , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Fibra de Algodão , Filtração/estatística & dados numéricos , Humanos , Exposição por Inalação , Nanopartículas , Tamanho da Partícula , Permeabilidade , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Dióxido de Silício
9.
Cell ; 183(3): 730-738.e13, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-32979942

RESUMO

SARS-CoV-2 is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins, the detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryoelectron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in pre- and postfusion conformations were determined to average resolutions of 8.7-11 Å. Compositions of the N-linked glycans from the native spikes were analyzed by mass spectrometry, which revealed overall processing states of the native glycans highly similar to that of the recombinant glycoprotein glycans. The native conformation of the ribonucleoproteins (RNPs) and their higher-order assemblies were revealed. Overall, these characterizations revealed the architecture of the SARS-CoV-2 virus in exceptional detail and shed light on how the virus packs its ∼30-kb-long single-segmented RNA in the ∼80-nm-diameter lumen.


Assuntos
Betacoronavirus/fisiologia , Betacoronavirus/ultraestrutura , Montagem de Vírus , Animais , Chlorocebus aethiops , Microscopia Crioeletrônica , Humanos , Espectrometria de Massas , Modelos Moleculares , Conformação Proteica , Células Vero , Proteínas Virais/química , Proteínas Virais/ultraestrutura , Cultura de Vírus
10.
Cell ; 183(3): 739-751.e8, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-32991842

RESUMO

The SARS-CoV-2 spike (S) protein variant D614G supplanted the ancestral virus worldwide, reaching near fixation in a matter of months. Here we show that D614G was more infectious than the ancestral form on human lung cells, colon cells, and on cells rendered permissive by ectopic expression of human ACE2 or of ACE2 orthologs from various mammals, including Chinese rufous horseshoe bat and Malayan pangolin. D614G did not alter S protein synthesis, processing, or incorporation into SARS-CoV-2 particles, but D614G affinity for ACE2 was reduced due to a faster dissociation rate. Assessment of the S protein trimer by cryo-electron microscopy showed that D614G disrupts an interprotomer contact and that the conformation is shifted toward an ACE2 binding-competent state, which is modeled to be on pathway for virion membrane fusion with target cells. Consistent with this more open conformation, neutralization potency of antibodies targeting the S protein receptor-binding domain was not attenuated.


Assuntos
Betacoronavirus/fisiologia , Betacoronavirus/ultraestrutura , Glicoproteína da Espícula de Coronavírus/fisiologia , Glicoproteína da Espícula de Coronavírus/ultraestrutura , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Betacoronavirus/patogenicidade , Células Cultivadas , Infecções por Coronavirus/virologia , Feminino , Variação Genética , Células HEK293 , Humanos , Masculino , Modelos Moleculares , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Conformação Proteica , Processamento de Proteína Pós-Traducional , Receptores Virais/metabolismo , Especificidade da Espécie
11.
Curr Top Med Chem ; 20(26): 2362-2378, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32962613

RESUMO

The article highlights an up-to-date progress in studies on structural and the remedial aspects of novel coronavirus 2019-nCoV, renamed as SARS-CoV-2, leading to the disease COVID-19, a pandemic. In general, all CoVs including SARS-CoV-2 are spherical positive single-stranded RNA viruses containing spike (S) protein, envelope (E) protein, nucleocapsid (N) protein, and membrane (M) protein, where S protein has a Receptor-binding Domain (RBD) that mediates the binding to host cell receptor, Angiotensin Converting Enzyme 2 (ACE2). The article details the repurposing of some drugs to be tried for COVID-19 and presents the status of vaccine development so far. Besides drugs and vaccines, the role of Convalescent Plasma (CP) therapy to treat COVID-19 is also discussed.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Pandemias , Peptidil Dipeptidase A/química , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Glicoproteína da Espícula de Coronavírus/genética , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Betacoronavirus/ultraestrutura , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Expressão Gênica , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva/métodos , Ivermectina/uso terapêutico , Modelos Moleculares , Niclosamida/uso terapêutico , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Domínios e Motivos de Interação entre Proteínas/efeitos dos fármacos , Estrutura Secundária de Proteína , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Vírus da SARS/ultraestrutura , Síndrome Respiratória Aguda Grave , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/biossíntese
12.
Cell ; 182(6): 1560-1573.e13, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32783916

RESUMO

SARS-CoV-2 is the causative agent of the 2019-2020 pandemic. The SARS-CoV-2 genome is replicated and transcribed by the RNA-dependent RNA polymerase holoenzyme (subunits nsp7/nsp82/nsp12) along with a cast of accessory factors. One of these factors is the nsp13 helicase. Both the holo-RdRp and nsp13 are essential for viral replication and are targets for treating the disease COVID-19. Here we present cryoelectron microscopic structures of the SARS-CoV-2 holo-RdRp with an RNA template product in complex with two molecules of the nsp13 helicase. The Nidovirales order-specific N-terminal domains of each nsp13 interact with the N-terminal extension of each copy of nsp8. One nsp13 also contacts the nsp12 thumb. The structure places the nucleic acid-binding ATPase domains of the helicase directly in front of the replicating-transcribing holo-RdRp, constraining models for nsp13 function. We also observe ADP-Mg2+ bound in the nsp12 N-terminal nidovirus RdRp-associated nucleotidyltransferase domain, detailing a new pocket for anti-viral therapy development.


Assuntos
Metiltransferases/química , RNA Helicases/química , RNA Replicase/química , Proteínas não Estruturais Virais/química , Replicação Viral , Difosfato de Adenosina/química , Difosfato de Adenosina/metabolismo , Betacoronavirus/genética , Betacoronavirus/metabolismo , Betacoronavirus/ultraestrutura , Sítios de Ligação , Microscopia Crioeletrônica , Holoenzimas/química , Holoenzimas/metabolismo , Magnésio/metabolismo , Metiltransferases/metabolismo , Ligação Proteica , RNA Helicases/metabolismo , RNA Replicase/metabolismo , RNA Viral/química , Proteínas não Estruturais Virais/metabolismo
13.
Commun Biol ; 3(1): 374, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641750

RESUMO

The recent outbreak of infections and the pandemic caused by SARS-CoV-2 represent one of the most severe threats to human health in more than a century. Emerging data from the United States and elsewhere suggest that the disease is more severe in men. Knowledge gained, and lessons learned, from studies of the biological interactions and molecular links that may explain the reasons for the greater severity of disease in men, and specifically in the age group at risk for prostate cancer, will lead to better management of COVID-19 in prostate cancer patients. Such information will be indispensable in the current and post-pandemic scenarios.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Neoplasias da Próstata/epidemiologia , Distribuição por Sexo , Antineoplásicos Hormonais/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/fisiologia , Betacoronavirus/ultraestrutura , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Suscetibilidade a Doenças , Reposicionamento de Medicamentos , Feminino , Previsões , Hormônios Esteroides Gonadais/fisiologia , Humanos , Masculino , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/fisiologia , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Inibidores de Proteases/uso terapêutico , Receptores Virais/efeitos dos fármacos , Receptores Virais/fisiologia , Fatores de Risco , Serina Endopeptidases/biossíntese , Serina Endopeptidases/fisiologia , Estados Unidos/epidemiologia , Internalização do Vírus
14.
Infect Dis Poverty ; 9(1): 99, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32690096

RESUMO

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has caused a public catastrophe and global concern. The main symptoms of COVID-19 are fever, cough, myalgia, fatigue and lower respiratory tract infection signs. Almost all populations are susceptible to the virus, and the basic reproduction number (R0) is 2.8-3.9. The fight against COVID-19 should have two aspects: one is the treatment of infected patients, and the other is the mobilization of the society to avoid the spread of the virus. The treatment of patients includes supportive treatment, antiviral treatment, and oxygen therapy. For patients with severe acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) and circulatory support are recommended. Plasma therapy and traditional Chinese medicine have also achieved good outcomes. This review is intended to summarize the research on this new coronavirus, to analyze the similarities and differences between COVID-19 and previous outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and to provide guidance regarding new methods of prevention, diagnosis and clinical treatment based on autodock simulations. METHODS: This review compares the multifaceted characteristics of the three coronaviruses including COVID-19, SARS and MERS. Our researchers take the COVID-19, SARS, and MERS as key words and search literatures in the Pubmed database. We compare them horizontally and vertically which respectively means concluding the individual characteristics of each coronavirus and comparing the similarities and differences between the three coronaviruses. RESULTS: We searched for studies on each outbreak and their solutions and found that the main biological differences among SARS-CoV-2, SARS-CoV and MERS-CoV are in ORF1a and the sequence of gene spike coding protein-S. We also found that the types and severity of clinical symptoms vary, which means that the diagnosis and nursing measures also require differentiation. In addition to the common route of transmission including airborne transmission, these three viruses have their own unique routes of transmission such as fecal-oral route of transmission COVID-19. CONCLUSIONS: In evolutionary history, these three coronaviruses have some similar biological features as well as some different mutational characteristics. Their receptors and routes of transmission are not all the same, which makes them different in clinical features and treatments. We discovered through the autodock simulations that Met124 plays a key role in the efficiency of drugs targeting ACE2, such as remdesivir, chloroquine, ciclesonide and niclosamide, and may be a potential target in COVID-19.


Assuntos
Antivirais/química , Infecções por Coronavirus , Pandemias , Peptidil Dipeptidase A/química , Pneumonia Viral , Receptores Virais/química , Síndrome Respiratória Aguda Grave , Animais , Antivirais/metabolismo , Betacoronavirus/genética , Betacoronavirus/fisiologia , Betacoronavirus/ultraestrutura , Técnicas de Laboratório Clínico , Ensaios Clínicos como Assunto , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Reservatórios de Doenças , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Coronavírus da Síndrome Respiratória do Oriente Médio/ultraestrutura , Simulação de Acoplamento Molecular , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Pneumonia Viral/transmissão , Receptores Virais/metabolismo , Vírus da SARS/genética , Vírus da SARS/fisiologia , Vírus da SARS/ultraestrutura , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/transmissão
15.
Nature ; 584(7821): 450-456, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32698192

RESUMO

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continues, with devasting consequences for human lives and the global economy1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this coronavirus. Here we report the isolation of sixty-one SARS-CoV-2-neutralizing monoclonal antibodies from five patients infected with SARS-CoV-2 and admitted to hospital with severe coronavirus disease 2019 (COVID-19). Among these are nineteen antibodies that potently neutralized authentic SARS-CoV-2 in vitro, nine of which exhibited very high potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng ml-1. Epitope mapping showed that this collection of nineteen antibodies was about equally divided between those directed against the receptor-binding domain (RBD) and those directed against the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody that targets the RBD, a second that targets the NTD, and a third that bridges two separate RBDs showed that the antibodies recognize the closed, 'all RBD-down' conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Epitopos de Linfócito B/imunologia , Pneumonia Viral/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Monoclonais/análise , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/ultraestrutura , Anticorpos Neutralizantes/análise , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/ultraestrutura , Anticorpos Antivirais/análise , Anticorpos Antivirais/química , Anticorpos Antivirais/ultraestrutura , Betacoronavirus/química , Betacoronavirus/ultraestrutura , Infecções por Coronavirus/prevenção & controle , Microscopia Crioeletrônica , Modelos Animais de Doenças , Mapeamento de Epitopos , Epitopos de Linfócito B/química , Epitopos de Linfócito B/ultraestrutura , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fab das Imunoglobulinas/imunologia , Fragmentos Fab das Imunoglobulinas/ultraestrutura , Pulmão/patologia , Pulmão/virologia , Masculino , Mesocricetus , Modelos Moleculares , Testes de Neutralização , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Glicoproteína da Espícula de Coronavírus/ultraestrutura
16.
Viruses ; 12(7)2020 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-32605306

RESUMO

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), and norovirus (NV) are highly contagious pathogens that threaten human health. Here we focused on the antiviral potential of the medicinal herb, Saxifraga spinulosa (SS). Water-soluble extracts of SS were prepared, and their virus-inactivating activity was evaluated against the human virus pathogens SARS-CoV-2 and IAV; we also examined virucidal activity against feline calicivirus and murine norovirus, which are surrogates for human NV. Among our findings, we found that SS-derived gallocatechin gallate compounds were capable of inactivating all viruses tested. Interestingly, a pyrogallol-enriched fraction (Fr 1C) inactivated all viruses more rapidly and effectively than did any of the component compounds used alone. We found that 25 µg/mL of Fr 1C inactivated >99.6% of SARS-CoV-2 within 10 s (reduction of ≥2.33 log10 TCID50/mL). Fr 1C resulted in the disruption of viral genomes and proteins as determined by gel electrophoresis, electron microscopy, and reverse transcription-PCR. Taken together, our results reveal the potential of Fr 1C for development as a novel antiviral disinfectant.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Vírus da Influenza A/efeitos dos fármacos , Norovirus/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plantas Medicinais , Saxifragaceae , Betacoronavirus/ultraestrutura , Calicivirus Felino/efeitos dos fármacos , Eletroforese em Gel de Poliacrilamida , Genoma Viral/efeitos dos fármacos , Testes de Hemaglutinação , Humanos , Microscopia Eletrônica de Transmissão , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Virais/efeitos dos fármacos
17.
J Fr Ophtalmol ; 43(7): 642-652, 2020 Sep.
Artigo em Francês | MEDLINE | ID: mdl-32631687

RESUMO

The COVID-19 pandemic has dramatically changed our daily lives as ophthalmologists. This general review firstly provides a better understanding of the virus responsible for the pandemic: the SARS-CoV-2, and the clinical manifestations of the COVID-19 disease. The second part is detailing the pathophysiology, clinical signs and challenges of ocular involvement, which seems rare and not functionally severe, but which may be a potential source of contamination. Finally, we discuss the preventive measures that need to be implemented in our daily practice to avoid any viral dissemination.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções Oculares Virais/virologia , Pneumonia Viral/complicações , Betacoronavirus/genética , Betacoronavirus/ultraestrutura , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/prevenção & controle , Técnicas de Diagnóstico Oftalmológico , Olho/virologia , Infecções Oculares Virais/fisiopatologia , Infecções Oculares Virais/prevenção & controle , Genoma Viral , Humanos , Microscopia Eletrônica , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/prevenção & controle , Integração Viral
18.
Nat Struct Mol Biol ; 27(8): 763-767, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32647346

RESUMO

SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host. Here, we investigate the relationship of spike (S) glycoprotein from SARS-CoV-2 with the S protein of a closely related bat virus, RaTG13. We determined cryo-EM structures for RaTG13 S and for both furin-cleaved and uncleaved SARS-CoV-2 S; we compared these with recently reported structures for uncleaved SARS-CoV-2 S. We also biochemically characterized their relative stabilities and affinities for the SARS-CoV-2 receptor ACE2. Although the overall structures of human and bat virus S proteins are similar, there are key differences in their properties, including a more stable precleavage form of human S and about 1,000-fold tighter binding of SARS-CoV-2 to human receptor. These observations suggest that cleavage at the furin-cleavage site decreases the overall stability of SARS-CoV-2 S and facilitates the adoption of the open conformation that is required for S to bind to the ACE2 receptor.


Assuntos
Betacoronavirus/genética , Interações Hospedeiro-Patógeno/genética , Peptidil Dipeptidase A/química , Receptores Virais/química , Glicoproteína da Espícula de Coronavírus/química , Animais , Betacoronavirus/metabolismo , Betacoronavirus/ultraestrutura , Sítios de Ligação , Quirópteros/virologia , Infecções por Coronavirus/virologia , Microscopia Crioeletrônica , Evolução Molecular , Furina/química , Expressão Gênica , Células HEK293 , Humanos , Modelos Moleculares , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Estabilidade Proteica , Proteólise , Receptores Virais/genética , Receptores Virais/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Homologia Estrutural de Proteína
20.
ACS Nano ; 14(8): 9364-9388, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32667191

RESUMO

The SARS-Cov-2 pandemic has spread worldwide during 2020, setting up an uncertain start of this decade. The measures to contain infection taken by many governments have been extremely severe by imposing home lockdown and industrial production shutdown, making this the biggest crisis since the second world war. Additionally, the continuous colonization of wild natural lands may touch unknown virus reservoirs, causing the spread of epidemics. Apart from SARS-Cov-2, the recent history has seen the spread of several viral pandemics such as H2N2 and H3N3 flu, HIV, and SARS, while MERS and Ebola viruses are considered still in a prepandemic phase. Hard nanomaterials (HNMs) have been recently used as antimicrobial agents, potentially being next-generation drugs to fight viral infections. HNMs can block infection at early (disinfection, entrance inhibition) and middle (inside the host cells) stages and are also able to mitigate the immune response. This review is focused on the application of HNMs as antiviral agents. In particular, mechanisms of actions, biological outputs, and limitations for each HNM will be systematically presented and analyzed from a material chemistry point-of-view. The antiviral activity will be discussed in the context of the different pandemic viruses. We acknowledge that HNM antiviral research is still at its early stage, however, we believe that this field will rapidly blossom in the next period.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/terapia , Nanoestruturas/uso terapêutico , Pandemias , Pneumonia Viral/terapia , Imunidade Adaptativa , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Betacoronavirus/ultraestrutura , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Sistemas de Liberação de Medicamentos , Fulerenos/uso terapêutico , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Humanos , Imunidade Inata , Nanopartículas Metálicas/uso terapêutico , Modelos Biológicos , Nanotecnologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Espécies Reativas de Oxigênio/uso terapêutico , Internalização do Vírus/efeitos dos fármacos
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