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2.
Ars pharm ; 61(2): 63-79, abr.-jun. 2020. tab, ilus, graf
Artículo en Español | IBECS | ID: ibc-188101

RESUMEN

INTRODUCCIÓN: En diciembre de 2019, se detectaron los primeros casos de enfermedad respiratoria causada por un coronavirus emergente, al que se denominó SARS-CoV-2, que en los primeros meses de 2020 se ha extendido por todo el mundo con características de pandemia. MÉTODO: Se examinaron las publicaciones más relevantes en relación con los objetivos de la revisión. RESULTADOS: La enfermedad, conocida como COVID-19, cursa con tos, fiebre y dificultad respiratoria. Las formas más graves, que afectan principalmente a personas de edad avanzada y con determinadas comorbilidades, se manifiestan por afectación de la función respiratoria, que requiere ventilación mecánica, y síndrome de respuesta inflamatoria sistémica, que puede conducir a un choque séptico con fallo multiorgánico, y altas tasas de mortalidad. En esta revisión se examina el estado actual de conocimientos sobre las características y origen del SARS-CoV-2, su replicación, y la patogénesis, clínica, diagnóstico, tratamiento y prevención de COVID-19. CONCLUSIONES: Las características del SARS-CoV-2 y la clínica de COVID-19 son bien conocidas. La PCR es la técnica de referencia para el diagnóstico de laboratorio; se dispone de ensayos para detección de antígenos y de anticuerpos, con margen de optimización. Los protocolos de tratamiento incluyen la corrección de la respuesta inflamatoria sistémica y administración de agentes antivirales. Existen vacunas en desarrollo


INTRODUCTION: In December 2019, the first cases of respiratory disease caused by an emerging coronavirus were detected. The causative agento f the outbreak was called SARS-CoV-2, and in the first months of 2020 it spread throughout the world as a pandemic. METHOD: The most relevant publications concerned with the aims of the review were examined. RESULTS: The disease, known as COVID-19. Patients show cough, fever, and respiratory distress. The most severe forms, mainly affecting the elderly and associated with various comorbidities, are manifested by impaired respiratory function, requiring mechanical ventilation, and systemic inflammatory response syndrome, which can lead to septic shock with multi-organ failure and high mortality rates. This review examines the current state of knowledge about the characteristics and origin of SARS-CoV-2, its replication, and the pathogenesis, clinical, diagnosis, treatment, and prevention of COVID-19. CONCLUSIONS: The characteristics of SARS-CoV-2 and the clinical manifestations of COVID-19 are well known. PCR is the reference technique for laboratory diagnosis; assays for the detection of antigens and antibodies are available, with optimization possibilities. Treatment protocols include attenuation of the systemic inflammatory response and administration of antiviral agents. There are vaccines in development


Asunto(s)
Humanos , Infecciones por Coronavirus , Neumonía Viral , Betacoronavirus/patogenicidad , Pandemias , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/terapia , Neumonía Viral/diagnóstico , Neumonía Viral/prevención & control , Neumonía Viral/terapia
3.
Ars pharm ; 61(2): 145-148, abr.-jun. 2020.
Artículo en Español | IBECS | ID: ibc-188102

RESUMEN

El coronavirus 2019 (SARS-CoV-2) ha sido declarado una emergencia de salud pública de impacto internacional por la Organización Mundial de la Salud. Debido a la aparición repentina de este proceso pandémico asociado con alta morbilidad y la mortalidad en todo el mundo, se han implementado varios tratamientos en los pacientes aquejados con esta dolencia. En este marco, comenzaron a usarse en pacientes críticos altas dosis de vitamina C. En este trabajo, analizamos los ensayos clínicos y / o trabajos de investigación disponibles en la literatura. Aunque se necesita más evidencia sobre su efectividad, es importante que el especialista comprenda la lógica clínica de este uso para determinar si es correcto como tratamiento concomitante. Conclusiones: El uso de altas dosis de vitamina C por vía parenteral parece ser una alternativa segura, disponible y económica, especialmente para pacientes críticos


The 2019 coronavirus (SARS-CoV-2) has been declared a public health emergency of international concern by the World Health Organization. Due to the sudden appearance of this pandemic process associated with increasing morbidity and mortality worldwide, various treatments have been implemented. In this framework, high doses of vitamin C began to be used in critically ill patients. We analyze the clinical trials and/or research papers available in the literature. Although more evidence on its effectiveness is needed is important for the specialist to understand the clinical logic of this use to determine if it is correct as a concomitant treatment. Conclusions: It seems that using high doses of vitamin C parenterally is a safe, available and economical alternative especially for critically ill patients


Asunto(s)
Humanos , Ácido Ascórbico/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Betacoronavirus , Pandemias , Medicina Basada en la Evidencia , Ensayos Clínicos como Asunto , Infusiones Parenterales , Enfermedad Crítica
5.
Physiother Theory Pract ; : 1-5, 2020 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-32406778

RESUMEN

The pandemic spread of coronavirus disease 2019 (COVID-19) has driven efforts to address the global threat to public health and there is increasing pressure to exploit interventions to manage the pneumonic inflammation manifested in this disease. Ultra-shortwave diathermy (USWD) is proposed by some rehabilitation professions in China, purportedly to minimise pneumonic inflammation. However, treatment of any symptomatic pneumonia should be evidence-based. There is no valid evidence, published in English, which establishes any benefit of USWD in pulmonary conditions, let alone COVID-19. The need for rigorous research and evidence-based practice is discussed in this article. Novel interventions require a solid physiological basis and must undergo rigorous testing prior to clinical adoption even during a pandemic. We are of the view that deployment of USWD in patients with COVID-19 must be prudent and supported by a logical scientific basis.

6.
Transpl Infect Dis ; : e13326, 2020 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-32406985

RESUMEN

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic that is evolving rapidly at present with unprecedented global health and societal implications. Herein, we report a case of successful treatment of SARS-CoV-2 induced inflammatory syndrome by utilization of the interleukin-6 receptor antagonist (IL-6Ra) tocilizumab.

7.
J Med Virol ; 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32356910

RESUMEN

The recent emergence of coronavirus disease 2019 (COVID-19) pandemic has reassessed the usefulness of historic convalescent plasma transfusion (CPT). This review was conducted to evaluate the effectiveness of CPT therapy in COVID-19 patients based on the publications reported till date. To our knowledge, this is the first systematic review on convalescent plasma on clinically relevant outcomes in individuals with COVID-19. PubMed, EMBASE, and Medline databases were searched upto 19 April 2020. All records were screened as per the protocol eligibility criteria. We included five studies reporting CPT to COVID-19 patients. The main findings from available data are as follows: (a) Convalescent plasma may reduce mortality in critically ill patients, (b) Increase in neutralizing antibody titers and disappearance of SARS-CoV-2 RNA was observed in almost all the patients after CPT therapy, and (c) Beneficial effect on clinical symptoms after administration of convalescent plasma. Based on the limited scientific data, CPT therapy in COVID-19 patients appears safe, clinically effective, and reduces mortality. Well-designed large multicenter clinical trial studies should be conducted urgently to establish the efficacy of CPT to COVID-19 patients.

8.
Stem Cells Dev ; 2020 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-32380908

RESUMEN

This prospective nonrandomized open-label cohort study addresses the safety and efficacy of exosomes (ExoFlo™) derived from allogeneic bone marrow mesenchymal stem cells as treatment for severe COVID-19. During April 2020, ExoFlo was provided to 24 SARS-CoV-2 polymerase chain reaction-positive patients at a single hospital center, all of whom met criteria for severe COVID-19 as well as moderate-to-severe acute respiratory distress syndrome. Patients received a single 15 mL intravenous dose of ExoFlo and were evaluated for both safety and efficacy from days 1 to 14 post-treatment. All safety endpoints were met with no adverse events observed within 72 h of ExoFlo administration. A survival rate of 83% was observed. In total, 17 of 24 (71%) patients recovered, 3 of 24 (13%) patients remained critically ill though stable, and 4 of 24 (16%) patients expired for reasons unrelated to the treatment. Overall, after one treatment, patients' clinical status and oxygenation improved with an average pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) increase of 192% (P < 0.001). Laboratory values revealed significant improvements in absolute neutrophil count [mean reduction 32% (P value <0.001)] and lymphopenia with average CD3+, CD4+, and CD8+ lymphocyte counts increasing by 46% (P < 0.05), 45% (P < 0.05), and 46% (P < 0.001), respectively. Likewise, acute phase reactants declined, with mean C-reactive protein, ferritin, and D-dimer reduction of 77% (P < 0.001), 43% (P < 0.001), and 42% (P < 0.05), respectively. In conclusion, owing to its safety profile, capacity to restore oxygenation, downregulate cytokine storm, and reconstitute immunity, ExoFlo is a promising therapeutic candidate for severe COVID-19. Future randomized controlled trials (RCTs) are needed to determine ExoFlo therapeutic potential.

9.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(3): 279-286, 2020 Mar.
Artículo en Chino | MEDLINE | ID: mdl-32385990

RESUMEN

OBJECTIVE: To discuss the research progress in the field of coronavirus (CoVs) treatment based on the visualization analysis of knowledge graph. METHODS: The related literatures in the field of CoVs treatment were retrieved from the establishment of Web of Science core collection database to February 15th, 2020, and the literature analysis tool of Web of Science database was used to count the annual trend of published literatures. The VOSviewer software was used to analyze the relationship among countries, institutions, authors, clustering and density of subject words. The HistCite software was used to screen important documents and to draw the evolution process of hot spots. The CiteSpace software was used to analyze the breakout points of subject words, so as to find the front and hot spots in this field. RESULTS: A total of 1 747 data were retrieved, with the exception of 17 duplicate data, and 1 730 data were retained for visualization analysis. In terms of literature volume, the literatures on CoVs therapy rose after 2003 and 2012, and the number of published literatures had remained high since 2014. In terms of countries, the main countries that carried out the research on the treatment of CoVs were the United States (n = 613), China (n = 582), Germany (n = 122), Canada (n = 99), etc., and the cooperation among countries was close. In terms of institutions, the number of papers issued by Chinese Academy of Sciences in the field of CoVs treatment ranked first (n = 82), followed by University of Hong Kong of China (n = 74) and Chinese University of Hong Kong of China (n = 58), followed by National Institute of Allergy and Infectious Diseases (n = 37), and the cooperation among various institutions was close. In terms of literature authors, there were two high-yielding authors in the United States [Ralph S. Baric (n = 21) and Kuochen Chou (n = 17)], two Chinese authors [Yuen Kwok-yung (n = 17) and Jiang Shibo (n = 16)] and one Dutch author [Eric J. Snijder (n = 17)]. In terms of the cluster analysis of authors, the authors were closely related in reverse genetics, respiratory infection, receptor binding domain, etc., and the 15 top-cited papers came mainly from China, the United States, Netherlands and other countries, and the literature content represented the frontiers and hot spots in different periods. The treatment hot spots focused on preventing virus adsorption, inhibiting the virus gene nucleic acid replication, transcription and translation. The main subject words were divided into three main categories, namely, CoVs epidemiology, basic research and drug development, in which basic research and drug development were strongly correlated. In the subject words breakthrough analysis, there were time-related breakthrough points in 1991, 1996 and 2002, and the "diagnosis" and "sequence" were continuous hot spots. CONCLUSIONS: Through the visualization analysis of knowledge graph, the development trend and hot spots of CoVs therapy research could be well observed. In this study, the degree of attention in the field of CoVs treatment showed periodic changes, related to the outbreak of new CoVs, and the country, institutions and the author were closely related. The treatment hot spots focused on preventing virus adsorption, inhibiting the virus gene nucleic acid replication, transcription and translation in order to develop new targets of drug.


Asunto(s)
Infecciones por Coronavirus/terapia , Coronavirus , Bibliometría , China , Bases de Datos Factuales , Humanos , Pandemias , Reconocimiento de Normas Patrones Automatizadas , Neumonía Viral , Publicaciones , Estados Unidos
10.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 147-157, 2020 May 25.
Artículo en Chino | MEDLINE | ID: mdl-32391658

RESUMEN

The current epidemic situation of coronavirus disease 2019 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance" strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinary personalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in 10%patients' blood samples at acute period and 50%of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifying cytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance" strategy effectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviral effects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favored the balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short period of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased probiotics such as Lactobacillus and Bifidobacterium, so nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore,we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.


Asunto(s)
Infecciones por Coronavirus , Manejo de la Enfermedad , Pandemias , Neumonía Viral , Betacoronavirus/aislamiento & purificación , China/epidemiología , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/virología , Diagnóstico Precoz , Heces/virología , Humanos , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Neumonía Viral/virología , Esputo/virología
11.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 209-214, 2020 May 25.
Artículo en Chino | MEDLINE | ID: mdl-32391666

RESUMEN

OBJECTIVE: To analyze the roles of multidisciplinary team (MDT) in the diagnosis and treatment of suspected cases of coronavirus disease 2019 (COVID-19). METHODS: The clinical data of 48 patients with suspected COVID-19 admitted in Jinhua Municipal Central Hospital from January 21, 2020 to March 20, 2020 were retrospectively analyzed. RESULTS: In the 48 suspected cases, 18 were diagnosed with COVID-19, and 30 were excluded. Each of the confirmed cases were discussed among MDT for 2 to 12 times with an average of (4.7±3.2) times; while for non-COVID-19 patients were discussed for 2 to 4 times with an average of (2.3±0.6) times. With the guidance of MDT, one COVID-19 patient was transferred to designated provincial hospital after effective treatment; one patient complicated with acute cholecystitis underwent gallbladder puncture and drainage; and COVID-19 was excluded in a highly suspected patient after alveolar lavage fluid examination. Except one transferred patient, all 17 confirmed COVID-19 patients were cured and discharged. There was no cross-infection occurred in suspected patients during the hospitalization. There were no deaths and no medical staff infections. CONCLUSIONS: The efficiency of diagnosis and treatment for suspected COVID-19 patients can be improved with MDT, particularly for complicated cases.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus , Comunicación Interdisciplinaria , Pandemias , Grupo de Atención al Paciente , Neumonía Viral , Betacoronavirus/aislamiento & purificación , China , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/terapia , Humanos , Grupo de Atención al Paciente/normas , Neumonía Viral/diagnóstico , Neumonía Viral/terapia , Estudios Retrospectivos , Resultado del Tratamiento
12.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 232-239, 2020 May 25.
Artículo en Chino | MEDLINE | ID: mdl-32391670

RESUMEN

Acute respiratory failure due to acute hypoxemia is the major manifestation in severe coronavirus disease 2019 (COVID-19). Rational and effective respiratory support is crucial in the management of COVID-19 patients. High-flow nasal cannula (HFNC) has been utilized widely due to its superiority over other non-invasive respiratory support techniques. To avoid HFNC failure and intubation delay, the key issues are proper patients, timely application and improving compliance. It should be noted that elder patients are vulnerable for failed HFNC. We applied HFNC for oxygen therapy in severe and critical ill COVID-19 patients and summarized the following experiences. Firstly, to select the proper size of nasal catheter, to locate it at suitable place, and to confirm the nose and the upper respiratory airway unobstructed. Secondly, an initial ow of 60 L/min and 37℃ should be given immediately for patients with obvious respiratory distress or weak cough ability; otherwise, low-level support should be given first and the level gradually increased. Thirdly, to avoid hypoxia or hypoxemia, the treatment goal of HFNC should be maintained the oxygen saturation (SpO2) above 95% for patients without chronic pulmonary disease. Finally, patients should wear a surgical mask during HFNC treatment to reduce the risk of virus transmission through droplets or aerosols.


Asunto(s)
Infecciones por Coronavirus/terapia , Oxígeno , Neumonía Viral/terapia , Anciano , Betacoronavirus/aislamiento & purificación , Cánula , Humanos , Oxígeno/administración & dosificación , Pandemias
13.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 245-248, 2020 May 25.
Artículo en Chino | MEDLINE | ID: mdl-32391672

RESUMEN

OBJECTIVE: To explore the feasibility of radical resection for cancer patients complicated with coronavirus disease 2019 (COVID-19). METHODS: The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed. RESULTS: The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice. CONCLUSIONS: The case indicates that radical resection can be performed in SARS-CoV-2 patients with twice-negative SARS-CoV-2 nucleic acid testing results.


Asunto(s)
Neoplasias del Colon , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Betacoronavirus/aislamiento & purificación , Neoplasias del Colon/complicaciones , Neoplasias del Colon/cirugía , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/terapia , Manejo de la Enfermedad , Humanos , Neumonía Viral/complicaciones , Neumonía Viral/terapia , Resultado del Tratamiento
14.
Ned Tijdschr Geneeskd ; 1642020 Mar 11.
Artículo en Holandés | MEDLINE | ID: mdl-32391999

RESUMEN

Since the outbreak of COVID-19, chloroquine has been mentioned as a possible treatment. In vitro studies have shown anti-viral activity of chloroquine against SARS-CoV-2. Recently, the Dutch National Institute for Public Health and the Environment published treatment options for antiviral treatment for COVID-19 where chloroquine was suggested as first choice for off-label treatment, beside remdesivir en lopinavir/ritonavir. In this commentary, we provide a background and history of chloroquine, the evidence for antiviral efficacy of chloroquine and the arguments for off-label use of chloroquine in COVID-19.

15.
J Biomol Struct Dyn ; : 1-26, 2020 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-32396769

RESUMEN

The pandemic caused by novel coronavirus disease 2019 (COVID-19) infecting millions of populations worldwide and counting, has demanded quick and potential therapeutic strategies. Current approved drugs or molecules under clinical trials can be a good pool for repurposing through in-silico techniques to quickly identify promising drug candidates. The structural information of recently released crystal structures of main protease (Mpro) in APO and complex with inhibitors, N3, and 13b molecules was utilized to explore the binding site architecture through Molecular dynamics (MD) simulations. The stable state of Mpro was used to conduct extensive virtual screening of the aforementioned drug pool. Considering the recent success of HIV protease molecules, we also used anti-protease molecules for drug repurposing purposes. The identified top hits were further evaluated through MD simulations followed by the binding free energy calculations using MM-GBSA. Interestingly, in our screening, several promising drugs stand out as potential inhibitors of Mpro. However, based on control (N3 and 13b), we have identified six potential molecules, Leupeptin Hemisulphate, Pepstatin A, Nelfinavir, Birinapant, Lypression and Octreotide which have shown the reasonably significant MM-GBSA score. Further insight shows that the molecules form stable interactions with hot-spot residues, that are mainly conserved and can be targeted for structure- and pharmacophore-based designing. The pharmacokinetic annotations and therapeutic importance have suggested that these molecules possess drug-like properties and pave their way for in-vitro studies.

16.
J Biomol Struct Dyn ; : 1-10, 2020 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-32396771

RESUMEN

The pandemic of COVID-19 (Coronavirus Disease-2019) is an extremely contagious respiratory illness due to a novel coronavirus, SARS-CoV-2. Certain drugs have several protein targets and many illnesses share overlapping molecular paths. In such cases, reusing drugs for more than one objective and finding their novice uses can considerably decrease the time in finding new cures for unforeseen diseases .Remdesivir has been recently a strong candidate for the treatment of Covid-19. In this commentary, we have portrayed the structure of the coronavirus in a simple way as well as the site where remdesivir acts. We have also displayed the ongoing clinical trials, as well as a published study that was conducted on compassionate base.The covid-19 pandemic might wean down by the end of summer 2020, but the risk of seasonality exists. Therefore, future disposal of agents such as remdesivir might be crucial for ensuring an efficient treatment, decrease mortality and allow early discharge.

17.
J Biomol Struct Dyn ; : 1-17, 2020 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-32396773

RESUMEN

The current pandemic of Covid-19 caused by SARS-CoV-2 is continued to spread globally and no potential drug or vaccine against it is available. Spike (S) glycoprotein is the structural protein of SARS-CoV-2 located on the envelope surface, involve in interaction with angiotensin converting enzyme 2 (ACE2), a cell surface receptor, followed by entry into the host cell. Thereby, blocking the S glycoprotein through potential inhibitor may interfere its interaction with ACE2 and impede its entry into the host cell. Here, we present a truncated version of human ACE2 (tACE2), comprising the N terminus region of the intact ACE2 from amino acid position 21-119, involved in binding with receptor binding domain (RBD) of SARS-CoV-2. We analyzed the in-silico potential of tACE2 to compete with intact ACE2 for binding with RBD. The protein-protein docking and molecular dynamic simulation showed that tACE2 has higher binding affinity for RBD and form more stabilized complex with RBD than the intact ACE2. Furthermore, prediction of tACE2 soluble expression in E. coli makes it a suitable candidate to be targeted for Covid-19 therapeutics. This is the first MD simulation based findings to provide a high affinity protein inhibitor for SARS-CoV-2 S glycoprotein, an important target for drug designing against this unprecedented challenge.

18.
Am J Perinatol ; 2020 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-32396947

RESUMEN

Hypertensive disorders are the most common medical complications of pregnancy and a major cause of maternal and perinatal morbidity and death. The detection of elevated blood pressure during pregnancy is one of the cardinal aspects of optimal antenatal care. With the outbreak of novel coronavirus disease 2019 (COVID-19) and the risk for person-to-person spread of the virus, there is a desire to minimize unnecessary visits to health care facilities. Women should be classified as low risk or high risk for hypertensive disorders of pregnancy and adjustments can be accordingly made in the frequency of maternal and fetal surveillance. During this pandemic, all pregnant women should be encouraged to obtain a sphygmomanometer. Patients monitored for hypertension as an outpatient should receive written instructions on the important signs and symptoms of disease progression and provided contact information to report the development of any concern for change in status. As the clinical management of gestational hypertension and preeclampsia is the same, assessment of urinary protein is unnecessary in the management once a diagnosis of a hypertensive disorder of pregnancy is made. Pregnant women with suspected hypertensive disorders of pregnancy and signs and symptoms associated with the severe end of the disease spectrum (e.g., headaches, visual symptoms, epigastric pain, and pulmonary edema) should have an evaluation including complete blood count, serum creatinine level, and liver transaminases (aspartate aminotransferase and alanine aminotransferase). Further, if there is any evidence of disease progression or if acute severe hypertension develops, prompt hospitalization is suggested. Current guidelines from the American College of Obstetricians and Gynecologists (ACOG) and The Society for Maternal-Fetal Medicine (SMFM) for management of preeclampsia with severe features suggest delivery after 34 0/7 weeks of gestation. With the outbreak of COVID-19, however, adjustments to this algorithm should be considered including delivery by 30 0/7 weeks of gestation in the setting of preeclampsia with severe features. KEY POINTS: · Outbreak of novel coronavirus disease 2019 (COVID-19) warrants fewer office visits.. · Women should be classified for hypertension risk in pregnancy.. · Earlier delivery suggested with COVID-19 and hypertensive disorder..

19.
Platelets ; : 1-6, 2020 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-32397915

RESUMEN

Coronavirus disease 2019 (COVID-19) is a new infectious disease that currently lacks standardized and established laboratory markers to evaluate its severity. In COVID-19 patients, the number of platelets (PLTs) and dynamic changes of PLT-related parameters are currently a concern. The present paper discusses the potential link between PLT parameters and COVID-19. Several studies have identified a link between severe COVID-19 patients and specific coagulation index, in particular, high D-dimer level, prolonged prothrombin time, and low PLT count. These alterations reflect the hypercoagulable state present in severe COVID-19 patients, which could promote microthrombosis in the lungs, as well as in other organs. Further information and more advanced hematological parameters related to PLTs are needed to better estimate this link, also considering COVID-19 patients at different disease stages and stratified in different cohorts based on preexisting co-morbidity, age, and gender. Increasing the understanding of PLT functions in COVID-19 will undoubtedly improve our knowledge on disease pathogenesis, clinical management, and therapeutic options, but could also lead to the development of more precise therapeutic strategies for COVID-19 patients.

20.
RNA ; 2020 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-32398273

RESUMEN

As the COVID-19 outbreak spreads, there is a growing need for a compilation of conserved RNA genome regions in the SARS-CoV-2 virus along with their structural propensities to guide development of antivirals and diagnostics. Here we present a first look at RNA sequence conservation and structural propensities in the SARS-CoV-2 genome. Using sequence alignments spanning a range of betacoronaviruses, we rank genomic regions by RNA sequence conservation, identifying 79 regions of length at least 15 nucleotides as exactly conserved over SARS-related complete genome sequences available near the beginning of the COVID-19 outbreak. We then confirm the conservation of the majority of these genome regions across 739 SARS-CoV-2 sequences subsequently reported from the COVID-19 outbreak, and we present a curated list of 30 'SARS-related-conserved' regions. We find that known RNA structured elements curated as Rfam families and in prior literature are enriched in these conserved genome regions, and we predict additional conserved, stable secondary structures across the viral genome. We provide 106 'SARS-CoV-2-conserved-structured' regions as potential targets for antivirals that bind to structured RNA. We further provide detailed secondary structure models for the extended 5' UTR, frame-shifting element, and 3' UTR. Last, we predict regions of the SARS-CoV-2 viral genome that have low propensity for RNA secondary structure and are conserved within SARS-CoV-2 strains. These 59 'SARS-CoV-2-conserved-unstructured' genomic regions may be most easily targeted in primer-based diagnostic and oligonucleotide-based therapeutic strategies.

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