RESUMEN
Coronavirus spike proteins mediate receptor binding and membrane fusion, making them prime targets for neutralizing antibodies. In the cases of severe acute respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus, spike proteins transition freely between open and closed conformations to balance host cell attachment and immune evasion1-5. Spike opening exposes domain S1B, allowing it to bind to proteinaceous receptors6,7, and is also thought to enable protein refolding during membrane fusion4,5. However, with a single exception, the pre-fusion spike proteins of all other coronaviruses studied so far have been observed exclusively in the closed state. This raises the possibility of regulation, with spike proteins more commonly transitioning to open states in response to specific cues, rather than spontaneously. Here, using cryogenic electron microscopy and molecular dynamics simulations, we show that the spike protein of the common cold human coronavirus HKU1 undergoes local and long-range conformational changes after binding a sialoglycan-based primary receptor to domain S1A. This binding triggers the transition of S1B domains to the open state through allosteric interdomain crosstalk. Our findings provide detailed insight into coronavirus attachment, with possibilities of dual receptor usage and priming of entry as a means of immune escape.
Asunto(s)
Betacoronavirus , Polisacáridos , Ácidos Siálicos , Glicoproteína de la Espiga del Coronavirus , Humanos , Regulación Alostérica , Betacoronavirus/química , Betacoronavirus/ultraestructura , Resfriado Común/virología , Microscopía por Crioelectrón , Simulación de Dinámica Molecular , Polisacáridos/química , Polisacáridos/metabolismo , Unión Proteica , Conformación Proteica , Ácidos Siálicos/química , Ácidos Siálicos/metabolismo , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/ultraestructura , Evasión InmuneRESUMEN
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.
Introducción. El nuevo coronavirus causante de un brote de enfermedad respiratoria aguda en China en diciembre de 2019 se identificó como SARS-CoV-2. La enfermedad, denominada COVID-19, fue declarada pandemia por la Organización Mundial de la Salud (OMS). El primer caso de COVID-19 en Colombia se reportó el 6 de marzo de 2020; en este estudio se caracterizó un aislamiento temprano del virus SARS-CoV-2 de una muestra ecolectada en abril de 2020. Objetivos. Describir y caracterizar una cepa temprana a partir de un aislamiento de SARSCoV-2 durante la pandemia en Colombia. Materiales y métodos. Se obtuvo una muestra de un paciente con COVID-19 confirmada por qRT-PCR; la muestra fue inoculada en diferentes líneas celulares hasta la aparición del efecto citopático. Para confirmar la presencia de SARS-CoV-2 en el cultivo, se utilizó la qRT-PCR a partir de los sobrenadantes, la inmunofluorescencia indirecta (IFI) en células Vero-E6, así como microscopía electrónica y secuenciación de nueva generación (nextgeneration sequencing). Resultados. Se confirmó el aislamiento de SARS-CoV-2 en células Vero-E6 por la aparición del efecto citopático tres días después de la infección, así como mediante la qRT-PCR y la IFI positiva con suero de paciente convaleciente positivo para SARS-CoV-2. Además, en las imágenes de microscopía electrónica de trasmisión y de barrido de células infectadas se observaron estructuras compatibles con viriones de SARS-CoV-2. Por último, se obtuvo la secuencia completa del genoma, lo que permitió clasificar el aislamiento como linaje B.1.5. Conclusiones. La evidencia presentada en este artículo permite confirmar el primer aislamiento de SARS-CoV-2 en Colombia. Además, muestra que esta cepa se comporta en cultivo celular de manera similar a lo reportado en la literatura para otros aislamientos y que su composición genética está acorde con la variante predominante en el mundo. Finalmente, se resalta la importancia que tiene el aislamiento viral para la detección de anticuerpos, para la caracterización genotípica y fenotípica de la cepa y para probar compuestos con potencial antiviral.
Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/virología , Pandemias , Neumonía Viral/virología , ARN Viral/genética , Animales , Betacoronavirus/genética , Betacoronavirus/fisiología , Betacoronavirus/ultraestructura , COVID-19 , Chlorocebus aethiops , Colombia/epidemiología , Convalecencia , Infecciones por Coronavirus/epidemiología , Efecto Citopatogénico Viral , Técnica del Anticuerpo Fluorescente Indirecta , Genoma Viral , Humanos , Microscopía Electrónica , Tipificación Molecular , Nasofaringe/virología , Neumonía Viral/epidemiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2 , Análisis de Secuencia de ARN , Especificidad de la Especie , Células Vero , Virión/ultraestructura , Cultivo de VirusRESUMEN
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.
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Bromelaínas/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Fitoterapia , Neumonía Viral/tratamiento farmacológico , Ananas , Betacoronavirus/ultraestructura , Bromelaínas/farmacología , COVID-19 , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Interacciones Huésped-Patógeno , Humanos , Pandemias , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Neumonía Viral/virología , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19RESUMEN
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.
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Betacoronavirus/fisiología , Infecciones por Coronavirus/inmunología , Interacciones Huésped-Patógeno/inmunología , Neumonía Viral/inmunología , Betacoronavirus/ultraestructura , COVID-19 , Infecciones por Coronavirus/virología , Humanos , Pandemias , Neumonía Viral/virología , SARS-CoV-2 , Proteínas Estructurales Virales/fisiologíaRESUMEN
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.
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Betacoronavirus/ultraestructura , Desinfectantes/farmacología , Propiolactona/farmacología , Virión/efectos de los fármacos , Animales , Betacoronavirus/efectos de los fármacos , Betacoronavirus/inmunología , Vacunas contra la COVID-19 , Chlorocebus aethiops , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Microscopía por Crioelectrón , Tomografía con Microscopio Electrónico , Humanos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/ultraestructura , Vacunas de Productos Inactivados/inmunología , Células Vero , Vacunas Virales/inmunología , Virión/ultraestructuraRESUMEN
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.
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Betacoronavirus/ultraestructura , Infecciones por Coronavirus/transmisión , Interacciones Huésped-Patógeno/fisiología , Neumonía Viral/transmisión , Animales , COVID-19 , Línea Celular , Chlorocebus aethiops , Infecciones por Coronavirus/patología , Humanos , Microscopía Electrónica de Rastreo , Pandemias , Neumonía Viral/patología , SARS-CoV-2 , Células VeroRESUMEN
Abordaje Cardiovascular durante la COVID-19 Dra Susana Blanco
Asunto(s)
Betacoronavirus/inmunología , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Pandemias/prevención & control , Infecciones por Coronavirus/inmunología , Neumonía Viral/inmunología , Anomalías Cardiovasculares/virología , Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Capacitación de Recursos Humanos en Salud , Personal de Salud/educación , Cardiopatías/virología , Betacoronavirus/ultraestructura , Infecciones por Coronavirus/transmisión , Neumonía Viral/transmisión , Interferones/inmunología , Fenómenos del Sistema Inmunológico/fisiologíaRESUMEN
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 â¼30-kb-long single-segmented RNA in the â¼80-nm-diameter lumen.
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Betacoronavirus/fisiología , Betacoronavirus/ultraestructura , Ensamble de Virus , Animales , Chlorocebus aethiops , Microscopía por Crioelectrón , Humanos , Espectrometría de Masas , Modelos Moleculares , Conformación Proteica , SARS-CoV-2 , Células Vero , Proteínas Virales/química , Proteínas Virales/ultraestructura , Cultivo de VirusRESUMEN
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.
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Betacoronavirus , Infecciones por Coronavirus/prevención & control , Filtración/instrumentación , Máscaras , Pandemias/prevención & control , Neumonía Viral/prevención & control , Dispositivos de Protección Respiratoria , Textiles , Aerosoles , Microbiología del Aire , Betacoronavirus/ultraestructura , COVID-19 , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Fibra de Algodón , Filtración/estadística & datos numéricos , Humanos , Exposición por Inhalación , Nanopartículas , Tamaño de la Partícula , Permeabilidad , Neumonía Viral/transmisión , Neumonía Viral/virología , SARS-CoV-2 , Dióxido de SilicioRESUMEN
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.
Asunto(s)
Betacoronavirus/fisiología , Betacoronavirus/ultraestructura , Glicoproteína de la Espiga del Coronavirus/fisiología , Glicoproteína de la Espiga del Coronavirus/ultraestructura , Enzima Convertidora de Angiotensina 2 , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Betacoronavirus/patogenicidad , COVID-19 , Células Cultivadas , Infecciones por Coronavirus/virología , Femenino , Variación Genética , Células HEK293 , Humanos , Masculino , Modelos Moleculares , Pandemias , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/virología , Conformación Proteica , Procesamiento Proteico-Postraduccional , Receptores de Coronavirus , Receptores Virales/metabolismo , SARS-CoV-2 , Especificidad de la EspecieRESUMEN
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.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Pandemias , Peptidil-Dipeptidasa A/química , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Glicoproteína de la Espiga del Coronavirus/genética , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Enzima Convertidora de Angiotensina 2 , Betacoronavirus/efectos de los fármacos , Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , Betacoronavirus/ultraestructura , COVID-19 , Vacunas contra la COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Expresión Génica , Interacciones Huésped-Patógeno/efectos de los fármacos , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Hidroxicloroquina/uso terapéutico , Inmunización Pasiva/métodos , Ivermectina/uso terapéutico , Modelos Moleculares , Niclosamida/uso terapéutico , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/inmunología , Neumonía Viral/diagnóstico , Neumonía Viral/inmunología , Dominios y Motivos de Interacción de Proteínas/efectos de los fármacos , Estructura Secundaria de Proteína , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/efectos de los fármacos , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/patogenicidad , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/ultraestructura , SARS-CoV-2 , Síndrome Respiratorio Agudo Grave , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas Virales/biosíntesis , Sueroterapia para COVID-19RESUMEN
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.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus , Nanotecnología/métodos , Pandemias , Neumonía Viral , Antivirales/administración & dosificación , Betacoronavirus/química , Betacoronavirus/ultraestructura , COVID-19 , Prueba de COVID-19 , Vacunas contra la COVID-19 , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/terapia , Desinfección/métodos , Humanos , Nanopartículas/química , Nanopartículas/ultraestructura , Nanoestructuras/química , Nanotecnología/legislación & jurisprudencia , Pandemias/prevención & control , Patentes como Asunto , Neumonía Viral/diagnóstico , Neumonía Viral/prevención & control , Neumonía Viral/terapia , SARS-CoV-2 , Propiedades de Superficie , Vacunas Virales/administración & dosificaciónAsunto(s)
Betacoronavirus/ultraestructura , Infecciones por Coronavirus/patología , Células Epiteliales/ultraestructura , Células Epiteliales/virología , Neumonía Viral/patología , Bronquios/citología , COVID-19 , Células Cultivadas , Humanos , Microscopía Electrónica de Rastreo , Pandemias , SARS-CoV-2 , Cultivo de VirusRESUMEN
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.
Asunto(s)
Metiltransferasas/química , ARN Helicasas/química , ARN Polimerasa Dependiente del ARN/química , Proteínas no Estructurales Virales/química , Replicación Viral , Adenosina Difosfato/química , Adenosina Difosfato/metabolismo , Betacoronavirus/genética , Betacoronavirus/metabolismo , Betacoronavirus/ultraestructura , Sitios de Unión , ARN Polimerasa Dependiente de ARN de Coronavirus , Microscopía por Crioelectrón , Holoenzimas/química , Holoenzimas/metabolismo , Magnesio/metabolismo , Metiltransferasas/metabolismo , Unión Proteica , ARN Helicasas/metabolismo , ARN Viral/química , ARN Polimerasa Dependiente del ARN/metabolismo , SARS-CoV-2 , Proteínas no Estructurales Virales/metabolismoRESUMEN
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.
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Antivirales/química , Infecciones por Coronavirus , Pandemias , Peptidil-Dipeptidasa A/química , Neumonía Viral , Receptores Virales/química , Síndrome Respiratorio Agudo Grave , Enzima Convertidora de Angiotensina 2 , Animales , Antivirales/metabolismo , Betacoronavirus/genética , Betacoronavirus/fisiología , Betacoronavirus/ultraestructura , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico , Ensayos Clínicos como Asunto , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/transmisión , Reservorios de Enfermedades , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Coronavirus del Síndrome Respiratorio de Oriente Medio/fisiología , Coronavirus del Síndrome Respiratorio de Oriente Medio/ultraestructura , Simulación del Acoplamiento Molecular , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Neumonía Viral/transmisión , Receptores de Coronavirus , Receptores Virales/metabolismo , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/fisiología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/ultraestructura , SARS-CoV-2 , Síndrome Respiratorio Agudo Grave/diagnóstico , Síndrome Respiratorio Agudo Grave/epidemiología , Síndrome Respiratorio Agudo Grave/transmisión , Tratamiento Farmacológico de COVID-19RESUMEN
INTRODUCTION: COVID-19 is caused by the coronavirus SARS-CoV-2. Ocular manifestations have been reported including conjunctivitis and retinal changes. Therefore, it is of the utmost importance to clarify eye involvement in COVID-19 in order to help with its diagnosis and to further prevent its transmission. The purpose of this review is to describe the structure and transmission of SARS-CoV-2, reported ocular findings and protection strategies for ophthalmologists. MATERIAL AND METHODS: Literature search on PubMed for relevant articles using the keywords 'COVID-19', 'coronavirus', and 'SARS-CoV-2' in conjunction with 'ophthalmology' and 'eye'. Moreover, official recommendations of ophthalmological societies were reviewed. RESULTS: Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of the ocular surface and upper respiratory tract are connected by the nasolacrimal duct, the eye is rarely involved in human SARS-CoV-2 infection and the SARS-CoV-2 RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with COVID-19 is also extremely low. DISCUSSION: The eye can be affected by SARS-CoV-2, which is supported by some reports of conjunctivitis and retinal changes, but its role in the spread of the disease is still unknown. CONCLUSION: Given the current scarce evidence, more research is needed to clarify the relationship between SARS-CoV-2 and the eye.
Introdução: COVID-19 é o nome atribuído à doença causada pelo novo coronavírus - SARS-CoV-2. Esta infeção rapidamente atingiu uma disseminação mundial, face ao aumento da globalização e adaptação do vírus a ambientes distintos. Foram descritas manifestações oftalmológicas em doentes com COVID-19, nomeadamente, conjuntivite e alterações retinianas. Assim, é fundamental esclarecer o envolvimento ocular na COVID-19, contribuindo para o seu diagnóstico precoce e limitando a sua transmissão. O objetivo desta revisão é descrever a estrutura e o modo de transmissão do SARS-CoV-2, assim como manifestações oculares reportadas e estratégias de proteção para oftalmologistas. Material e Métodos: Revisão dos artigos relevantes publicados na PubMed usando as palavras-chave 'COVID-19', 'coronavirus' e 'SARS-CoV-2' em associação com as palavras 'ophthalmology' e 'eye'. Além disso, foi feita uma revisão das recomendações oficiais de várias sociedades oftalmológicas a nível mundial. Resultados: Apesar da conjuntiva estar diretamente exposta a patógenos exógenos, e da mucosa da superfície ocular e do trato respiratório superior estarem conectados pelo canal nasolacrimal, o olho raramente parece ser afetado pelo SARS-CoV-2. A infeção por SARS-CoV-2 e a taxa de positividade para a pesquisa do RNA do SARS-CoV-2 pelo teste de RT-PCR em lágrimas e secreções conjuntivais de pacientes com COVID-19 também são extremamente baixas. Discussão: O olho pode ser afetado pelo SARS-CoV-2, dada a descrição de casos de conjuntivite e alterações retinianas, mas o seu papel na disseminação da doença ainda é desconhecido. Conclusão: Dada a escassa evidência atual, são necessários mais estudos para esclarecer a relação entre o SARS-CoV-2 e o globo ocular.
Asunto(s)
Betacoronavirus , Conjuntiva/virología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Oftalmología/normas , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , Anciano , Antivirales/uso terapéutico , Betacoronavirus/genética , Betacoronavirus/ultraestructura , COVID-19 , Cloroquina/uso terapéutico , Conjuntivitis Viral/virología , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Desinfección/normas , Seguridad de Equipos , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Masculino , Máscaras , Persona de Mediana Edad , Equipo de Protección Personal , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Guías de Práctica Clínica como Asunto , ARN Viral/aislamiento & purificación , Receptor de Angiotensina Tipo 2 , SARS-CoV-2RESUMEN
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.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/complicaciones , Infecciones Virales del Ojo/virología , Neumonía Viral/complicaciones , Betacoronavirus/genética , Betacoronavirus/ultraestructura , COVID-19 , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/prevención & control , Técnicas de Diagnóstico Oftalmológico , Ojo/virología , Infecciones Virales del Ojo/fisiopatología , Infecciones Virales del Ojo/prevención & control , Genoma Viral , Humanos , Microscopía Electrónica , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/fisiopatología , Neumonía Viral/prevención & control , SARS-CoV-2 , Integración ViralRESUMEN
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.
Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Epítopos de Linfocito B/inmunología , Neumonía Viral/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunología , Animales , Anticuerpos Monoclonales/análisis , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/ultraestructura , Anticuerpos Neutralizantes/análisis , Anticuerpos Neutralizantes/química , Anticuerpos Neutralizantes/ultraestructura , Anticuerpos Antivirales/análisis , Anticuerpos Antivirales/química , Anticuerpos Antivirales/ultraestructura , Betacoronavirus/química , Betacoronavirus/ultraestructura , COVID-19 , Infecciones por Coronavirus/prevención & control , Microscopía por Crioelectrón , Modelos Animales de Enfermedad , Mapeo Epitopo , Epítopos de Linfocito B/química , Epítopos de Linfocito B/ultraestructura , Femenino , Humanos , Fragmentos Fab de Inmunoglobulinas/química , Fragmentos Fab de Inmunoglobulinas/inmunología , Fragmentos Fab de Inmunoglobulinas/ultraestructura , Pulmón/patología , Pulmón/virología , Masculino , Mesocricetus , Modelos Moleculares , Pruebas de Neutralización , Pandemias/prevención & control , Neumonía Viral/prevención & control , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/ultraestructuraRESUMEN
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.
Asunto(s)
Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Virus de la Influenza A/efectos de los fármacos , Norovirus/efectos de los fármacos , Extractos Vegetales/farmacología , Plantas Medicinales , Saxifragaceae , Betacoronavirus/ultraestructura , Calicivirus Felino/efectos de los fármacos , Electroforesis en Gel de Poliacrilamida , Genoma Viral/efectos de los fármacos , Pruebas de Hemaglutinación , Humanos , Microscopía Electrónica de Transmisión , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2 , Proteínas Virales/efectos de los fármacosRESUMEN
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.