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1.
EBioMedicine ; 57: 102847, 2020 Jun 20.
Artículo en Inglés | MEDLINE | ID: covidwho-612818
2.
Aging (Albany NY) ; 122020 Jun 16.
Artículo en Inglés | MEDLINE | ID: covidwho-601536

RESUMEN

The outbreak of COVID-19 has now become a global pandemic that has severely impacted lives and economic stability. There is, however, no effective antiviral drug that can be used to treat COVID-19 to date. Built on the fact that SARS-CoV-2 initiates its entry into human cells by the receptor binding domain (RBD) of its spike protein binding to the angiotensin-converting enzyme 2 (hACE2), we extended a recently developed approach, EvoDesign, to design multiple peptide sequences that can competitively bind to the SARS-CoV-2 RBD to inhibit the virus from entering human cells. The protocol starts with the construction of a hybrid peptidic scaffold by linking two fragments grafted from the interface of the hACE2 protein (a.a. 22-44 and 351-357) with a linker glycine, which is followed by the redesign and refinement simulations of the peptide sequence to optimize its binding affinity to the interface of the SARS-CoV-2 RBD. The binding experiment analyses showed that the designed peptides exhibited a significantly stronger binding potency to hACE2 than the wild-type hACE2 receptor (with -53.35 vs. -46.46 EvoEF2 energy unit scores for the top designed and wild-type peptides, respectively). This study demonstrates a new avenue to utilize computationally designed peptide motifs to treat the COVID-19 disease by blocking the critical spike-RBD and hACE2 interactions.

3.
Brief Bioinform ; 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: covidwho-459209

RESUMEN

The outbreak caused by the novel coronavirus SARS-CoV-2 has been declared a global health emergency. G-quadruplex structures in genomes have long been considered essential for regulating a number of biological processes in a plethora of organisms. We have analyzed and identified 25 four contiguous GG runs (G2NxG2NyG2NzG2) in the SARS-CoV-2 RNA genome, suggesting putative G-quadruplex-forming sequences (PQSs). Detailed analysis of SARS-CoV-2 PQSs revealed their locations in the open reading frames of ORF1 ab, spike (S), ORF3a, membrane (M) and nucleocapsid (N) genes. Identical PQSs were also found in the other members of the Coronaviridae family. The top-ranked PQSs at positions 13385 and 24268 were confirmed to form RNA G-quadruplex structures in vitro by multiple spectroscopic assays. Furthermore, their direct interactions with viral helicase (nsp13) were determined by microscale thermophoresis. Molecular docking model suggests that nsp13 distorts the G-quadruplex structure by allowing the guanine bases to be flipped away from the guanine quartet planes. Targeting viral helicase and G-quadruplex structure represents an attractive approach for potentially inhibiting the SARS-CoV-2 virus.

4.
Sleep Med ; 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: covidwho-457298

RESUMEN

BACKGROUND: An outbreak of the 2019 novel coronavirus (COVID-19) has been ongoing in China since January 2020. The threat of infection affects the work and life of most of the population and may also damage sleep. This study aims to examine the subjective sleep status and mental health of the population during the peak of the COVID-19 epidemic. METHOD: The data were collected through an online questionnaire with a sample of 5461 individuals in China from February 5, 2020, to February 23, 2020. Participants were divided into four groups based on their degree of threat from COVID-19: Group 1 was most closely associated with COVID-19, including inpatients diagnosed with COVID-19, first-line hospital workers and first-line management staff; Group 2 included outpatients diagnosed with COVID-19 and patients who developed a fever and visited the hospital; Group 3 included people related to Group 1 or 2, such as their colleagues, relatives, friends and rescuers; and Group 4 was the farthest removed from contact with COVID-19, covering the general public affected by COVID-19 prevention strategies. The Insomnia Severity Index (ISI), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7) and Acute Stress Disorder Scale (ASDS) were used. RESULTS: Threat degree of COVID-19 (groups) had significant correlations with insomnia, depression, anxiety, and stress (p < 0.05, p < 0.01). Age, gender, and area (Hubei province or other provinces) had significant correlations with insomnia (p < 0.01). A total of 1380 (24.46%) participants were suspected of having major depression based on the PHQ-9. Additionally, 1042 (18.47%) participants were suspected of having generalized anxiety disorder based on the GAD-7. A total of 892 (15.8%) of the participants had Acute Stress Disorder (ASD) according to the ASDS. The prevalence of clinical insomnia during the outbreak was 20.05% (1131) according to the ISI. The factors of satisfaction with the current sleep pattern and how perceptible the symptoms of the current sleep pattern are to other people (p < 0.05) and the middle (difficulty staying asleep) and terminal (waking up too early) (p < 0.01) factors of the ISI were significantly different across groups. A total of 1129 (20.01%) participants spent more than one hour awake in bed. CONCLUSION: The results indicated that insomnia is more severe in people who are female, young, living in the epicenter and experiencing a high degree of threat from COVID-19. As prevention and treatment efforts continue with regard to COVID-19, the general public has developed poor sleep hygiene habits, which deserve attention.

5.
Front Cardiovasc Med ; 2020.
Artículo | COVIDWHO | ID: covidwho-337046

RESUMEN

In December 2019, Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2, occurred in China and has currently led to a global pandemic In addition to respiratory involvement, COVID-19 was also associated with significant multiple organ dysfunction syndrome (MODS) Cardiovascular impairment has been observed and is now drawing growing attention Cardiovascular protective strategies are urgent and of great significance to the overall prognosis of COVID-19 patients Direct viral infection, cytokine storm, and aggravation of existing cardiovascular diseases were recognized as possible mechanisms of cardiovascular impairment in COVID-19 Hyperactivated inflammation plays an important role in all three mechanisms and is considered to be fundamental in the development of cardiovascular impairment and MODS in COVID-19 Therefore, in addition to conventional cardiovascular treatment, anti-inflammatory therapy is a reasonable strategy for severe cases to further enhance cardiovascular protection and potentially mitigate MODS We reviewed the inflammatory features and current promising treatments of COVID-19 as well as cardiovascular anti-inflammatory therapies that have been verified in previous clinical trials with positive outcomes We believe that targeting the central pathway (IL-1beta, TNF-alpha, IL-6), balancing the Th1 and Th2 response, and administering long-term anti-inflammatory therapy might be promising prospects to reduce cardiovascular impairment and even MODS during the acute and recovery phases of COVID-19 The cardiovascular anti-inflammatory therapies might be of great application value to the management of COVID-19 patients and we further propose an algorithm for the selection of anti-inflammatory therapy for COVID-19 patients with or at high risk of cardiovascular impairment We recommend to take the experiences in cardiovascular anti-inflammatory therapy as references in the management of COVID-19 and conduct related clinical trials, while the clinical translation of novel treatments from preclinical studies or in vitro drug screening should proceed with caution due to unguaranteed efficacy and safety profiles

6.
Diabetes Obes Metab ; 2020 May 14.
Artículo en Inglés | MEDLINE | ID: covidwho-260543

RESUMEN

AIM: To explore whether coronavirus disease 2019 (COVID-19) patients with diabetes and secondary hyperglycaemia have different clinical characteristics and prognoses than those without significantly abnormal glucose metabolism. MATERIALS AND METHODS: We retrospectively analysed 166 COVID-19 patients at Tongji Hospital (Wuhan) from 8 February to 21 March 2020. Clinical characteristics and outcomes (as of 4 April 2020) were compared among control (group 1), secondary hyperglycaemia (group 2: no diabetes history, fasting plasma glucose levels of ≥7.0 mmol/L once and HbA1c values <6.5%) and patients with diabetes (group 3). RESULTS: Compared with group 1, groups 2 and 3 had higher rates of leukocytosis, neutrophilia, lymphocytopenia, eosinopenia and levels of hypersensitive C-reactive protein, ferritin and d-dimer (P < .05 for all). Group 2 patients had higher levels of lactate dehydrogenase, prevalence of liver dysfunction and increased interleukin-8 (IL-8) than those in group 1, and a higher prevalence of increased IL-8 was found in group 2 than in group 3 (P < .05 for all). The proportions of critical patients in groups 2 and 3 were significantly higher compared with group 1 (38.1%, 32.8% vs. 9.5%, P < .05 for both). Groups 2 and 3 had significantly longer hospital stays than group 1, which was nearly 1 week longer. The composite outcomes risks were 5.47 (1.56-19.82) and 2.61 (0.86-7.88) times greater in groups 2 and 3 than in group 1. CONCLUSIONS: Hyperglycaemia in both diabetes and secondary hyperglycaemia patients with COVID-19 may indicate poor prognoses. There were differences between patients with secondary hyperglycaemia and those with diabetes. We recommend that clinicians pay more attention to the blood glucose status of COVID-19 patients, even those not diagnosed with diabetes before admission.

8.
Ann Rheum Dis ; 2020 Apr 27.
Artículo en Inglés | MEDLINE | ID: covidwho-144087
9.
Mil Med Res ; 7(1): 19, 2020 04 20.
Artículo en Inglés | MEDLINE | ID: covidwho-72008

RESUMEN

Since December 2019, a novel type of coronavirus disease (COVID-19) in Wuhan led to an outbreak throughout China and the rest of the world. To date, there have been more than 1,260,000 COVID-19 patients, with a mortality rate of approximately 5.44%. Studies have shown that coagulation dysfunction is a major cause of death in patients with severe COVID-19. Therefore, the People's Liberation Army Professional Committee of Critical Care Medicine and Chinese Society on Thrombosis and Hemostasis grouped experts from the frontline of the Wuhan epidemic to come together and develop an expert consensus on diagnosis and treatment of coagulation dysfunction associated with a severe COVID-19 infection. This consensus includes an overview of COVID-19-related coagulation dysfunction, tests for coagulation, anticoagulation therapy, replacement therapy, supportive therapy and prevention. The consensus produced 18 recommendations which are being used to guide clinical work.


Asunto(s)
Betacoronavirus , Trastornos de la Coagulación Sanguínea/diagnóstico , Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Anciano , Anticoagulantes/uso terapéutico , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Trastornos de la Coagulación Sanguínea/virología , China , Consenso , Humanos , Persona de Mediana Edad , Pandemias
10.
J Thorac Cardiovasc Surg ; 2020 Apr 10.
Artículo en Inglés | MEDLINE | ID: covidwho-45786
12.
J Proteome Res ; 19(4): 1351-1360, 2020 04 03.
Artículo en Inglés | MEDLINE | ID: covidwho-11127

RESUMEN

As the infection of 2019-nCoV coronavirus is quickly developing into a global pneumonia epidemic, the careful analysis of its transmission and cellular mechanisms is sorely needed. In this Communication, we first analyzed two recent studies that concluded that snakes are the intermediate hosts of 2019-nCoV and that the 2019-nCoV spike protein insertions share a unique similarity to HIV-1. However, the reimplementation of the analyses, built on larger scale data sets using state-of-the-art bioinformatics methods and databases, presents clear evidence that rebuts these conclusions. Next, using metagenomic samples from Manis javanica, we assembled a draft genome of the 2019-nCoV-like coronavirus, which shows 73% coverage and 91% sequence identity to the 2019-nCoV genome. In particular, the alignments of the spike surface glycoprotein receptor binding domain revealed four times more variations in the bat coronavirus RaTG13 than in the Manis coronavirus compared with 2019-nCoV, suggesting the pangolin as a missing link in the transmission of 2019-nCoV from bats to human.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/virología , Genoma Viral/genética , Interacciones Huésped-Patógeno , Modelos Moleculares , Neumonía Viral/virología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Secuencia de Aminoácidos , Animales , Betacoronavirus/clasificación , Euterios/virología , VIH-1/genética , Humanos , Metagenoma , Pandemias , Estructura Terciaria de Proteína , Alineación de Secuencia , Análisis de Secuencia de Proteína , Serpientes/virología
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