Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 394
Filtrar
1.
J Transl Med ; 18(1): 222, 2020 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493510

RESUMEN

COVID-19 has rapidly spread all over the world, progressing into a pandemic. This situation has urgently impelled many companies and public research institutes to concentrate their efforts on research for effective therapeutics. Here, we outline the strategies and targets currently adopted in developing a vaccine against SARS-CoV-2. Based on previous evidence and experience with SARS and MERS, the primary focus has been the Spike protein, considered as the ideal target for COVID-19 immunotherapies.


Asunto(s)
Betacoronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/prevención & control , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas Virales/inmunología , Animales , Anticuerpos Antivirales/efectos adversos , Anticuerpos Antivirales/biosíntesis , Acrecentamiento Dependiente de Anticuerpo/inmunología , Betacoronavirus/genética , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/inmunología , Humanos , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Investigación en Medicina Traslacional , Vacunas Virales/efectos adversos , Vacunas Virales/genética
2.
BMJ ; 369: m2094, 2020 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493739

RESUMEN

OBJECTIVES: To describe the characteristics of children and adolescents affected by an outbreak of Kawasaki-like multisystem inflammatory syndrome and to evaluate a potential temporal association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: Prospective observational study. SETTING: General paediatric department of a university hospital in Paris, France. PARTICIPANTS: 21 children and adolescents (aged ≤18 years) with features of Kawasaki disease who were admitted to hospital between 27 April and 11 May 2020 and followed up until discharge by 15 May 2020. MAIN OUTCOME MEASURES: The primary outcomes were clinical and biological data, imaging and echocardiographic findings, treatment, and outcomes. Nasopharyngeal swabs were prospectively tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) and blood samples were tested for IgG antibodies to the virus. RESULTS: 21 children and adolescents (median age 7.9 (range 3.7-16.6) years) were admitted with features of Kawasaki disease over a 15 day period, with 12 (57%) of African ancestry. 12 (57%) presented with Kawasaki disease shock syndrome and 16 (76%) with myocarditis. 17 (81%) required intensive care support. All 21 patients had noticeable gastrointestinal symptoms during the early stage of illness and high levels of inflammatory markers. 19 (90%) had evidence of recent SARS-CoV-2 infection (positive RT-PCR result in 8/21, positive IgG antibody detection in 19/21). All 21 patients received intravenous immunoglobulin and 10 (48%) also received corticosteroids. The clinical outcome was favourable in all patients. Moderate coronary artery dilations were detected in 5 (24%) of the patients during hospital stay. By 15 May 2020, after 8 (5-17) days of hospital stay, all patients were discharged home. CONCLUSIONS: The ongoing outbreak of Kawasaki-like multisystem inflammatory syndrome among children and adolescents in the Paris area might be related to SARS-CoV-2. In this study an unusually high proportion of the affected children and adolescents had gastrointestinal symptoms, Kawasaki disease shock syndrome, and were of African ancestry.


Asunto(s)
Anticuerpos Antivirales/sangre , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Adolescente , Corticoesteroides/uso terapéutico , Betacoronavirus/genética , Betacoronavirus/inmunología , Niño , Preescolar , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/inmunología , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Masculino , Nasofaringe/virología , Pandemias , Paris , Neumonía Viral/complicaciones , Neumonía Viral/inmunología , Estudios Prospectivos , ARN Viral/genética , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/etiología
3.
Medicine (Baltimore) ; 99(23): e20661, 2020 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-32502054

RESUMEN

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is pandemic and is a medical issue. However, children account for a small portion of those with the disease, and there are few published reports of COVID-19 in children. The patient reported in this case report is the youngest case reported in Chengdu, China to date. PATIENT CONCERNS: A 3-month-old male infant presented with cough and rhinorrhea. DIAGNOSIS: Family members from Wuhan, the epicenter of the epidemic came to stay in the patient's home 16 days before the onset of his disease, and his mother had been diagnosed with COVID-19. He was diagnosed with COVID-19 based on a history of exposure and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), detected using reverse transcription polymerase chain reaction (RT-PCR). INTERVENTIONS: The patient was admitted to hospital and treated symptomatically with oral medication. OUTCOMES: The patient recovered completely and was discharged after one month of hospitalization. He tested negative for SARS-CoV-2 using RT-PCR and a chest CT performed 4 weeks after admission showed marked improvement prior to discharge. CONCLUSION: Clinicians must be aware of the presentation of COVID-19 in children because it differs from that in adults.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , Betacoronavirus/genética , Tos/etiología , Hospitalización , Humanos , Lactante , Masculino , Pandemias , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
4.
Viruses ; 12(6)2020 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-32503352

RESUMEN

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans; the second-largest and most deadly outbreak to date occurred in Saudi Arabia. The dromedary camel is considered a possible host of the virus and also to act as a reservoir, transmitting the virus to humans. Here, we studied evolutionary relationships for 31 complete genomes of betacoronaviruses, including eight newly sequenced MERS-CoV genomes isolated from dromedary camels in Saudi Arabia. Through bioinformatics tools, we also used available sequences and 3D structure of MERS-CoV spike glycoprotein to predict MERS-CoV epitopes and assess antibody binding affinity. Phylogenetic analysis showed the eight new sequences have close relationships with existing strains detected in camels and humans in Arabian Gulf countries. The 2019-nCov strain appears to have higher homology to both bat coronavirus and SARS-CoV than to MERS-CoV strains. The spike protein tree exhibited clustering of MERS-CoV sequences similar to the complete genome tree, except for one sequence from Qatar (KF961222). B cell epitope analysis determined that the MERS-CoV spike protein has 24 total discontinuous regions from which just six epitopes were selected with score values of >80%. Our results suggest that the virus circulates by way of camels crossing the borders of Arabian Gulf countries. This study contributes to finding more effective vaccines in order to provide long-term protection against MERS-CoV and identifying neutralizing antibodies.


Asunto(s)
Camelus/virología , Infecciones por Coronavirus/virología , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Glicoproteína de la Espiga del Coronavirus/genética , Secuencia de Aminoácidos , Animales , Betacoronavirus/clasificación , Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , Evolución Biológica , ADN Complementario/química , ADN Viral/química , Epítopos/análisis , Epítopos/química , Epítopos/genética , Biblioteca de Genes , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/clasificación , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Filogenia , ARN Viral/análisis , ARN Viral/química , ARN Viral/aislamiento & purificación , Arabia Saudita
5.
Theranostics ; 10(13): 5932-5942, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32483428

RESUMEN

On the 30th of January 2020, the World Health Organization fired up the sirens against a fast spreading infectious disease caused by a newly discovered Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and gave this disease the name COVID-19. While there is currently no specific treatment for COVID-19, several off label drugs approved for other indications are being investigated in clinical trials across the globe. In the last decade, theranostic nanoparticles were reported as promising tool for efficiently and selectively deliver therapeutic moieties (i.e. drugs, vaccines, siRNA, peptide) to target sites of infection. In addition, they allow monitoring infectious sides and treatment responses using noninvasive imaging modalities. While intranasal delivery was proposed as the preferred administration route for therapeutic agents against viral pulmonary diseases, NP-based delivery systems offer numerous benefits to overcome challenges associated with mucosal administration, and ensure that these agents achieve a concentration that is many times higher than expected in the targeted sites of infection while limiting side effects on normal cells. In this article, we have shed light on the promising role of nanoparticles as effective carriers for therapeutics or immune modulators to help in fighting against COVID-19.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/terapia , Nanopartículas/uso terapéutico , Neumonía Viral/terapia , Nanomedicina Teranóstica/métodos , Administración Intranasal , Antivirales/administración & dosificación , Betacoronavirus/efectos de los fármacos , Betacoronavirus/genética , Betacoronavirus/inmunología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Sistemas de Liberación de Medicamentos/métodos , Humanos , Nanopartículas/administración & dosificación , Nanopartículas/química , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Vacunas de Partículas Similares a Virus/administración & dosificación , Vacunas Virales/administración & dosificación , Vacunas Virales/inmunología , Internalización del Virus/efectos de los fármacos
6.
Molecules ; 25(11)2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32485894

RESUMEN

The coronavirus disease, COVID-19, caused by the novel coronavirus SARS-CoV-2, which first emerged in Wuhan, China and was made known to the World in December 2019 turned into a pandemic causing more than 126,124 deaths worldwide up to April 16th, 2020. It has 79.5% sequence identity with SARS-CoV-1 and the same strategy for host cell invasion through the ACE-2 surface protein. Since the development of novel drugs is a long-lasting process, researchers look for effective substances among drugs already approved or developed for other purposes. The 3D structure of the SARS-CoV-2 main protease was compared with the 3D structures of seven proteases, which are drug targets, and docking analysis to the SARS-CoV-2 protease structure of thirty four approved and on-trial protease inhibitors was performed. Increased 3D structural similarity between the SARS-CoV-2 main protease, the HCV protease and α-thrombin was found. According to docking analysis the most promising results were found for HCV protease, DPP-4, α-thrombin and coagulation Factor Xa known inhibitors, with several of them exhibiting estimated free binding energy lower than -8.00 kcal/mol and better prediction results than reference compounds. Since some of the compounds are well-tolerated drugs, the promising in silico results may warrant further evaluation for viral anticipation. DPP-4 inhibitors with anti-viral action may be more useful for infected patients with diabetes, while anti-coagulant treatment is proposed in severe SARS-CoV-2 induced pneumonia.


Asunto(s)
Anticoagulantes/química , Antivirales/química , Betacoronavirus/efectos de los fármacos , Inhibidores de la Dipeptidil-Peptidasa IV/química , Inhibidores de Proteasas/química , Proteínas no Estructurales Virales/antagonistas & inhibidores , Secuencia de Aminoácidos , Anticoagulantes/farmacología , Antivirales/farmacología , Betacoronavirus/química , Betacoronavirus/enzimología , Betacoronavirus/genética , Sitios de Unión , Infecciones por Coronavirus/tratamiento farmacológico , Cisteína Endopeptidasas/química , Cisteína Endopeptidasas/genética , Cisteína Endopeptidasas/metabolismo , Dipeptidil Peptidasa 4/química , Dipeptidil Peptidasa 4/genética , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Factor Xa/química , Factor Xa/genética , Factor Xa/metabolismo , Hepacivirus/química , Hepacivirus/enzimología , Hepacivirus/genética , Humanos , Simulación del Acoplamiento Molecular , Pandemias , Neumonía Viral/tratamiento farmacológico , Inhibidores de Proteasas/farmacología , Unión Proteica , Conformación Proteica , Dominios y Motivos de Interacción de Proteínas , Alineación de Secuencia , Homología Estructural de Proteína , Especificidad por Sustrato , Termodinámica , Trombina/antagonistas & inhibidores , Trombina/química , Trombina/genética , Trombina/metabolismo , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo
7.
Sci Transl Med ; 12(546)2020 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493791
8.
Indian J Public Health ; 64(Supplement): S147-S155, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32496247

RESUMEN

Background: The origin of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still a debatable topic. The association of the virus spread from the market is supported by the close relation of genome sequences of environmental surface samples with virus samples from earliest patients by phylogenetic analysis. Objectives: To have an insight into the SARS-CoV-2 genome sequences reported from India for better understanding on their epidemiology and virulence. Methods: Genome sequences of Indian isolates of SARS-CoV-2 were analyzed to understand their phylogeny and divergence with respect to other isolates reported from other countries. Amino acid sequences of individual open reading frames (ORFs) from SARS-CoV-2 Indian isolates were aligned with sequences of isolates reported from other countries to identify the mutations occurred in Indian isolates. Results: Our analysis suggests that Indian SARS-CoV-2 isolates are closely related to isolates reported from other parts of the world. Most ORFs are highly conserved; mutations were also detected in some ORFs. We found that most isolates reported from India have key mutations at 614th position of the S protein and 84th position of the ORF 8, which has been reported to be associated with high virulence and high transmission rate. Conclusion: An attempt was made to understand the SARS-CoV-2 virus reported from India. SARS-CoV-2 reported from India was closely similar to other SARS-CoV-2 reported from other parts of the world, which suggests that vaccines and other therapeutic methods generated from other countries might work well in India. In addition, available sequence data suggest that majority of Indian isolates are capable of high transmission and virulence.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/genética , Neumonía Viral/epidemiología , Neumonía Viral/genética , Humanos , India/epidemiología , Mutación , Sistemas de Lectura Abierta , Pandemias , Filogenia
9.
Vopr Virusol ; 65(1): 6-15, 2020.
Artículo en Ruso | MEDLINE | ID: mdl-32496715

RESUMEN

Results of analysis of phylogenetic, virological, epidemiological, ecological, clinical data of COVID-19 outbreaks in Wuhan, China (PRC) in comparison with SARS-2002 and MERS-2012 outbreaks allow to conclude: - the etiological agent of COVID-19 is coronavirus (2019-CoV), phylogenetically close to the SARS-CoV, isolated from human, and SARS-related viruses isolated from bats (SARS-related bat CoV viruses). These viruses belong to the Sarbecovirus subgenus, Betacoronavirus genus, Orthocoronavirinae subfamily, Coronaviridae family (Cornidovirinea: Nidovirales). COVID-19 is a variant of SARS-2002 and is different from MERS-2012 outbreak, which were caused by coronavirus belonged to the subgenus Merbecovirus of the same genus; - according to the results of phylogenetic analysis of 35 different betacoronaviruses, isolated from human and from wild animals in 2002-2019, the natural source of COVID-19 and SARS-CoV (2002) is bats of Rhinolophus genus (Rhinolophidae) and, probably, some species of other genera. An additional reservoir of the virus could be an intermediate animal species (snakes, civet, hedgehogs, badgers, etc.) that are infected by eating of infected bats. SARS-like coronaviruses circulated in bats in the interepidemic period (2003-2019); - seasonal coronaviruses (subgenus Duvinacovirus, Alphacoronavirus) are currently circulating (November 2019 - January 2020) in the European part of Russia, Urals, Siberia and the Far East of Russia, along with the influenza viruses A(H1N1)pdm09, A(H3N2), and В, as well as six other respiratory viruses (HPIV, HAdV, HRSV, HRV, HBoV, and HMPV).


Asunto(s)
Betacoronavirus/clasificación , Infecciones por Coronavirus/epidemiología , Pandemias , Filogenia , Neumonía Viral/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Animales , Betacoronavirus/genética , Betacoronavirus/patogenicidad , China/epidemiología , Quirópteros/virología , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/transmisión , Reservorios de Enfermedades/virología , Monitoreo Epidemiológico , Erizos/virología , Humanos , Mustelidae/virología , Neumonía Viral/diagnóstico , Neumonía Viral/fisiopatología , Neumonía Viral/transmisión , Salud Pública/estadística & datos numéricos , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/fisiopatología , Infecciones del Sistema Respiratorio/transmisión , Federación de Rusia/epidemiología , Serpientes/virología , Viverridae/virología
11.
Viruses ; 12(6)2020 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-32512929

RESUMEN

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a member of the betacoronavirus family, which causes COVID-19 disease. SARS-CoV-2 pathogenicity in humans leads to increased mortality rates due to alterations of significant pathways, including some resulting in exacerbated inflammatory responses linked to the "cytokine storm" and extensive lung pathology, as well as being linked to a number of comorbidities. Our current study compared five SARS-CoV-2 sequences from different geographical regions to those from SARS, MERS and two cold viruses, OC43 and 229E, to identify the presence of miR-like sequences. We identified seven key miRs, which highlight considerable differences between the SARS-CoV-2 sequences, compared with the other viruses. The level of conservation between the five SARS-CoV-2 sequences was identical but poor compared with the other sequences, with SARS showing the highest degree of conservation. This decrease in similarity could result in reduced levels of transcriptional control, as well as a change in the physiological effect of the virus and associated host-pathogen responses. MERS and the milder symptom viruses showed greater differences and even significant sequence gaps. This divergence away from the SARS-CoV-2 sequences broadly mirrors the phylogenetic relationships obtained from the whole-genome alignments. Therefore, patterns of mutation, occurring during sequence divergence from the longer established human viruses to the more recent ones, may have led to the emergence of sequence motifs that can be related directly to the pathogenicity of SARS-CoV-2. Importantly, we identified 7 key-microRNAs (miRs 8066, 5197, 3611, 3934-3p, 1307-3p, 3691-3p, 1468-5p) with significant links to KEGG pathways linked to viral pathogenicity and host responses. According to Bioproject data (PRJNA615032), SARS-CoV-2 mediated transcriptomic alterations were similar to the target pathways of the selected 7 miRs identified in our study. This mechanism could have considerable significance in determining the symptom spectrum of future potential pandemics. KEGG pathway analysis revealed a number of critical pathways linked to the seven identified miRs that may provide insight into the interplay between the virus and comorbidities. Based on our reported findings, miRNAs may constitute potential and effective therapeutic approaches in COVID-19 and its pathological consequences.


Asunto(s)
Betacoronavirus/genética , Genoma Viral/genética , MicroARNs/fisiología , Síndrome Respiratorio Agudo Grave/virología , Transducción de Señal/fisiología , Secuencia de Bases , Betacoronavirus/patogenicidad , Comorbilidad , Biología Computacional , Bases de Datos Genéticas , Humanos , MicroARNs/genética , Mutación , Alineación de Secuencia
12.
Emerg Microbes Infect ; 9(1): 1287-1299, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32525765

RESUMEN

A newly emerged coronavirus, SARS-CoV-2, caused severe pneumonia outbreaks in China in December 2019 and has since spread to various countries around the world. To trace the evolution route and probe the transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences available in the GISAID platform as of 5 March 2020. Among them, four genetic clusters, defined as super-spreaders (SSs), could be identified and were found to be responsible for the major outbreaks that subsequently occurred in various countries. SS1 was widely disseminated in Asia and the US, and mainly responsible for outbreaks in the states of Washington and California as well as South Korea, whereas SS4 contributed to the pandemic in Europe. Using the signature mutations of each SS as markers, we further analysed 1539 genome sequences reported after 29 February 2020 and found that 90% of these genomes belonged to SSs, with SS4 being the most dominant. The relative degree of contribution of each SS to the pandemic in different continents was also depicted. Identification of these super-spreaders greatly facilitates development of new strategies to control the transmission of SARS-CoV-2.


Asunto(s)
Betacoronavirus/genética , Brotes de Enfermedades , Síndrome Respiratorio Agudo Grave/virología , Betacoronavirus/clasificación , Betacoronavirus/patogenicidad , China/epidemiología , Análisis por Conglomerados , Bases de Datos Genéticas , Genoma Viral , Salud Global , Humanos , Mutación , Filogenia , Factores de Riesgo , Alineación de Secuencia , Análisis de Secuencia , Síndrome Respiratorio Agudo Grave/epidemiología , Síndrome Respiratorio Agudo Grave/transmisión , Virulencia
14.
Emerg Microbes Infect ; 9(1): 1397-1406, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32490731

RESUMEN

The ongoing severe acute respiratory syndrome pandemic caused by the novel coronavirus 2 (SARS-CoV-2) is associated with high morbidity and mortality rates, and it has created a pressing global need for effective antiviral therapies against it. COVID-19 disease pathogenesis is characterized by an initial virus-mediated phase, followed by inappropriate hyperactivation of the immune system leading to organ damage. Targeting of the SARS-CoV-2 viral receptors is being explored as a therapeutic option for these patients. In this paper, we summarize several potential receptors associated with the infectivity of SARS-CoV-2 and discuss their association with the immune-mediated inflammatory response. The potential for the development of resistance towards antiviral drugs is also presented. An algorithm-based platform to improve the efficacy of and overcome resistance to viral receptor blockers through the introduction of personalized variability is described. This method is designed to ensure sustained antiviral effectiveness when using SARS-CoV-2 receptor blockers.


Asunto(s)
Antivirales/farmacología , Betacoronavirus/fisiología , Infecciones por Coronavirus/inmunología , Farmacorresistencia Viral , Neumonía Viral/inmunología , Receptores Virales/antagonistas & inhibidores , Algoritmos , Animales , Betacoronavirus/efectos de los fármacos , Betacoronavirus/genética , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/virología , Humanos , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/genética , Neumonía Viral/virología , Receptores Virales/genética , Receptores Virales/inmunología
15.
Emerg Microbes Infect ; 9(1): 1415-1417, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32496967

RESUMEN

SARS-CoV-2, the causative agent of the COVID-19 pandemic, may be transmitted via airborne droplets or contact with surfaces onto which droplets have deposited. In this study, the ability of SARS-CoV-2 to survive in the dark, at two different relative humidity values and within artificial saliva, a clinically relevant matrix, was investigated. SARS-CoV-2 was found to be stable, in the dark, in a dynamic small particle aerosol under the four experimental conditions we tested and viable virus could still be detected after 90 minutes. The decay rate and half-life was determined and decay rates ranged from 0.4 to 2.27 % per minute and the half lives ranged from 30 to 177 minutes for the different conditions. This information can be used for advice and modelling and potential mitigation strategies.


Asunto(s)
Aerosoles/química , Betacoronavirus/crecimiento & desarrollo , Infecciones por Coronavirus/virología , Medios de Cultivo/química , Neumonía Viral/virología , Saliva Artificial/química , Salvia/virología , Microbiología del Aire , Betacoronavirus/química , Betacoronavirus/genética , Betacoronavirus/efectos de la radiación , Infecciones por Coronavirus/transmisión , Oscuridad , Humanos , Humedad , Cinética , Pandemias , Neumonía Viral/transmisión
16.
PLoS Biol ; 18(6): e3000715, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32511245

RESUMEN

Zoonotic coronavirus (CoV) infections, such as those responsible for the current severe acute respiratory syndrome-CoV 2 (SARS-CoV-2) pandemic, cause grave international public health concern. In infected cells, the CoV RNA-synthesizing machinery associates with modified endoplasmic reticulum membranes that are transformed into the viral replication organelle (RO). Although double-membrane vesicles (DMVs) appear to be a pan-CoV RO element, studies to date describe an assortment of additional CoV-induced membrane structures. Despite much speculation, it remains unclear which RO element(s) accommodate viral RNA synthesis. Here we provide detailed 2D and 3D analyses of CoV ROs and show that diverse CoVs essentially induce the same membrane modifications, including the small open double-membrane spherules (DMSs) previously thought to be restricted to gamma- and delta-CoV infections and proposed as sites of replication. Metabolic labeling of newly synthesized viral RNA followed by quantitative electron microscopy (EM) autoradiography revealed abundant viral RNA synthesis associated with DMVs in cells infected with the beta-CoVs Middle East respiratory syndrome-CoV (MERS-CoV) and SARS-CoV and the gamma-CoV infectious bronchitis virus. RNA synthesis could not be linked to DMSs or any other cellular or virus-induced structure. Our results provide a unifying model of the CoV RO and clearly establish DMVs as the central hub for viral RNA synthesis and a potential drug target in CoV infection.


Asunto(s)
Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Coronavirus/clasificación , Coronavirus/fisiología , Retículo Endoplásmico/patología , Retículo Endoplásmico/virología , Replicación Viral , Animales , Betacoronavirus/genética , Betacoronavirus/fisiología , Línea Celular , Chlorocebus aethiops , Tomografía con Microscopio Electrónico , Retículo Endoplásmico/ultraestructura , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/fisiología , Pandemias , Neumonía Viral/patología , Neumonía Viral/virología , ARN Viral/metabolismo , Células Vero
17.
J Phys Chem Lett ; 11(12): 4897-4900, 2020 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-32478523

RESUMEN

SARS-CoV-2, since emerging in Wuhan, China, has been a major concern because of its high infection rate and has left more than six million infected people around the world. Many studies endeavored to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV, in order to find solutions to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV spike (S) protein might be responsible for its higher affinity to the ACE2 human cell receptor. In this work, we used molecular dynamics simulations and Monte Carlo sampling to compare the binding affinities of the S proteins of SARS-CoV and SARS-CoV-2 to the ACE2. Our results show that the protein surface of the ACE2 at the receptor binding domain (RBD) exhibits negative electrostatic potential, while a positive potential is observed for the S proteins of SARS-CoV/SARS-CoV-2. In addition, the binding energies at the interface are slightly higher for SARS-CoV-2 because of enhanced electrostatic interactions. The major contributions to the electrostatic binding energies result from the salt bridges forming between R426 and ACE-2-E329 in the case of SARS-CoV and K417 and ACE2-D30 in the SARS-CoV-2. In addition, our results indicate that the enhancement in the binding energy is not due to a single mutant but rather because of the sophisticated structural changes induced by all these mutations together. This finding suggests that it is implausible for the SARS-CoV-2 to be a lab-engineered virus.


Asunto(s)
Betacoronavirus/química , Receptor de Angiotensina Tipo 2/química , Virus del SRAS/química , Betacoronavirus/efectos de los fármacos , Betacoronavirus/genética , Simulación por Computador , Infecciones por Coronavirus , Fenómenos Electrofisiológicos , Humanos , Modelos Moleculares , Simulación de Dinámica Molecular , Método de Montecarlo , Mutación/genética , Pandemias , Neumonía Viral , Receptor de Angiotensina Tipo 2/efectos de los fármacos , Receptor de Angiotensina Tipo 2/genética , Virus del SRAS/efectos de los fármacos , Virus del SRAS/genética
18.
Eur Rev Med Pharmacol Sci ; 24(10): 5772-5777, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32495914

RESUMEN

OBJECTIVE: It has recently been reported that some COVID-19 patients have long-term positive fecal nucleic acid after discharging from the hospital with negative nucleic acid in the respiratory tract, but it is unclear whether COVID-19 patients with positive long-term fecal nucleic acid tests have the risk of self-infection. PATIENTS AND METHODS: From January 25, 2020 to March 9, 2020, 5 COVID-19 patients with negative respiratory tract nucleic acid and positive fecal nucleic acid were observed and studied to explore whether these patients can re-infect themselves. Five patients with COVID-19 accompanied by diarrhea as the main gastrointestinal symptoms were carefully observed through clinical symptoms, imaging and other auxiliary examinations. The RT-PCR technology was used to continuously detect fecal and respiratory viral nucleic acids. The IgM antibody was detected on the 7th day of admission and IgM/IgG at the time of discharge. RESULTS: All 5 patients had symptoms of fever and diarrhea upon admission. The fecal nucleic acid was positive, as well as the throat swab was positive. All COVID-19 patients had positive IgM antibodies on the 7th day of admission and positive IgM and IgG at the time of discharge, and there were no abnormalities in the gastrointestinal examination on discharge. All 5 fecal nucleic acid tests were positive at the time of discharge. After continuous dynamic follow-up for 3-15 days, no clinical symptoms recurred, and the last nucleic acid test was negative. CONCLUSIONS: There is no risk of self-infection for COVID-19 patients with long-term 2019-nCoV nucleic acid positive in feces.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/diagnóstico , Heces/virología , Neumonía Viral/diagnóstico , ARN Viral/análisis , Adulto , Betacoronavirus/inmunología , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/virología , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Pandemias , Alta del Paciente , Faringe/virología , Neumonía Viral/virología , ARN Viral/genética , ARN Viral/metabolismo , Recurrencia , Tomografía Computarizada por Rayos X
19.
Eur Rev Med Pharmacol Sci ; 24(10): 5819-5829, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32495921

RESUMEN

In the 21st century, human civilization has witnessed three major epidemics caused by Coronaviruses namely severe acute respiratory syndrome coronavirus (SARS CoV) in 2003, Middle East respiratory syndrome coronavirus (MERS CoV) in 2012 and 2019 novel coronavirus (2019 nCoV) or coronavirus disease (COVID 19) in 2019. Among these, COVID-19 has greater transmission and mortality rate. 2019 nCoV belongs to a large family of positive sense single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species. The most communal symptoms of COVID-19 include fever, cough, and shortness of breath during the incubation period (2-14 days) of infection. COVID-19 transmission is occurring from infected humans to close contact with one another through respiratory droplets, coughs, and sneezes of infected person. Moreover, the virus containing surfaces may also transmit the infection. Diagnosis is being carried out by collecting a nasopharyngeal swab or sputum specimen for detection of SARS-CoV-2 RNA by reverse-transcription polymerase chain reaction (RT-PCR). Rapid diagnosing methods are also under development which can diagnose COVID 19 in few minutes to hours. Currently, there is no specific cure or preventive therapeutics available. Hence, based upon limited in-vitro and anecdotal data, Chloroquine, or Hydroxychloroquine, Remdesivir, Lopinavir and Ritonavir are being employed in the management. Search for new specific anti-viral drugs from natural/synthetic origins is under full swing and many of them are currently used as chemotherapeutic drugs under clinical investigation. Yet, there is a strong need for development of vaccine, which may take several months to few years for the development.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/patología , Neumonía Viral/patología , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Humanos , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , ARN Viral/genética , ARN Viral/metabolismo , Síndrome de Dificultad Respiratoria del Adulto/diagnóstico , Síndrome de Dificultad Respiratoria del Adulto/etiología , Análisis de Supervivencia
20.
Eur Rev Med Pharmacol Sci ; 24(10): 5830-5841, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32495923

RESUMEN

OBJECTIVE: Recent worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of respiratory coronavirus disease 2019 (COVID-19), is a current, ongoing life-threatening crisis, and international public health emergency. The early diagnosis and management of the disease remains a major challenge. In this review, we aim to summarize the updated epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus SARS-CoV-2. MATERIALS AND METHODS: A broad search of the literature was performed in "PubMed" "Medline" "Web of Science", "Google Scholar" and "World Health Organization-WHO" using the keywords "severe acute respiratory syndrome coronavirus", "2019-nCoV", "COVID-19, "SARS", "SARS-CoV-2" "Epidemiology" "Transmission" "Pathogenesis" "Clinical Characteristics". We reviewed and documented the information obtained from literature on epidemiology, pathogenesis and clinical appearances of SARS-CoV-2 infection. RESULTS: The global cases of COVID-19 as of April 2, 2020, have risen to more than 900,000 and morbidity has reached more than 47,000. The incidence rate for COVID-19 has been predicted to be higher than the previous outbreaks of other coronavirus family members, including those of SARS-CoV and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The main clinical presentation of SARS-CoV-2 infection ranges from asymptomatic stages to severe lower respiratory infection in the form of pneumonia. Most of the patients also presented with fever, cough, sore throat, headache, fatigue, myalgia and breathlessness. Individuals at higher risk for severe illness include elderly people and patients with a weakened immune system or that are suffering from an underlying chronic medical condition like hypertension, diabetes mellitus, cancer, respiratory illness or cardiovascular diseases. CONCLUSIONS: SARS-Cov-2 has emerged as a worldwide threat, currently affecting 170 countries and territories across the globe. There is still much to be understood regarding SARS-CoV-2 about its virology, epidemiology and clinical management strategies; this knowledge will be essential to both manage the current pandemic and to conceive comprehensive measures to prevent such outbreaks in the future.


Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/patología , Neumonía Viral/patología , Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , Líquido del Lavado Bronquioalveolar/virología , Comorbilidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/patología , Pandemias , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/virología , Cuarentena , ARN Viral/genética , ARN Viral/metabolismo , Esputo/virología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA