Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (21)

ProteinN (5)

ProteinE (3)

NSP5 (2)

ORF6 (1)


SARS-CoV-2 Proteins
    displaying 1 - 10 records in total 198
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    ADAM17 inhibition prevents neutrophilia MESHD and lung injury MESHD in a mouse model of Covid-19 MESHD

    Authors: Nathaniel L. Lartey; Salvador Valle-Reyes; Hilda Vargas-Robles; Karina E. Jiménez-Camacho; Idaira M. Guerrero-Fonseca; Ramón Castellanos-Martínez; Armando Montoya-García; Julio García-Cordero; Leticia Cedillo-Barrón; Porfirio Nava; Jessica G. Filisola-Villaseňor; Daniela Roa-Velázquez; Dan I. Zavala-Vargas; Edgar Morales-Ríos; Citlaltepetl Salinas-Lara; Eduardo Vadillo; Michael Schnoor

    doi:10.1101/2021.04.10.439288 Date: 2021-04-11 Source: bioRxiv

    Severe coronavirus disease MESHD coronavirus disease 2019 MESHD ( Covid-19 MESHD) is characterized by lung injury MESHD, cytokine storm and increased neutrophil-to-lymphocyte ratio (NLR). Current therapies focus on reducing viral replication and inflammatory responses, but no specific treatment exists to prevent the development of severe Covid-19 MESHD in infected individuals. Angiotensin-converting enzyme-2 ACE-2) is the receptor for SARS-CoV-2, the virus causing Covid-19 MESHD, but it is also critical for maintaining the correct functionality of lung epithelium and endothelium. Coronaviruses induce activation of a disintegrin and metalloprotease 17 (ADAM17) and shedding of ACE-2 from the cell surface resulting in exacerbated inflammatory responses. Thus, we hypothesized that ADAM17 inhibition ameliorates Covid-19 MESHD-related lung inflammation MESHD. We employed a pre-clinical mouse model using intra-tracheal instillation of a combination of polyinosinic:polycytidylic acid (poly-I:C) and the receptor-binding domain of the SARS-CoV-2 spike PROTEIN protein (RBD-S) to mimic lung damage MESHD associated with Covid-19 MESHD. Histological analysis of inflamed mice confirmed the expected signs of lung injury MESHD including edema MESHD, fibrosis MESHD, vascular congestion and leukocyte infiltration. Moreover, inflamed mice also showed an increased NLR as observed in critically ill Covid-19 MESHD patients. Administration of the ADAM17 inhibitors apratastat and TMI-1 significantly improved lung histology and prevented leukocyte infiltration. Reduced leukocyte recruitment could be explained by reduced production of pro-inflammatory cytokines and lower levels of the endothelial adhesion molecules ICAM-1 and VCAM-1. Additionally, the NLR was significantly reduced by ADAM17 inhibition. Thus, we propose inhibition of ADAM17 as a novel promising treatment strategy in SARS-CoV-2-infected MESHD individuals to prevent the progression towards severe Covid-19 MESHD.

    Sex differences in lung imaging and SARS-CoV-2 antibody responses in a COVID-19 MESHD golden Syrian hamster model

    Authors: Santosh Dhakal; Camilo A. Ruiz-Bedoya; Ruifeng Zhou; Patrick Creisher; Jason Villano; Kirsten Littlefield; Jennie Castillo; Paula Marinho; Anne Jedlicka; Alvaro Ordonez; Natalia Majewska; Michael Betenbaugh; Kelly Flavahan; Alice Mueller; Monika Looney; Darla Quijada; Filipa Mota; Sarah E. Beck; Jacqueline K Brockhurst; Alicia Braxton; Natalie Castell; Kelly A. Metcalf Pate; Petros C. Karakousis; Joseph L. Mankowski; Andrew Pekosz; Sanjay K Jain; Sabra L. Klein

    doi:10.1101/2021.04.02.438292 Date: 2021-04-04 Source: bioRxiv

    In the ongoing coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) MESHD, more severe outcomes are reported in males compared with females, including hospitalizations and deaths. Animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of SARS-CoV-2. Adult male and female golden Syrian hamsters (8-10 weeks of age) were inoculated intranasally with 105 TCID50 of SARS-CoV-2/USA-WA1/2020 and euthanized at several time points during the acute (i.e., virus actively replicating) and recovery (i.e., after the infectious virus has been cleared) phases of infection. There was no mortality, but infected male hamsters experienced greater morbidity, losing a greater percentage of body mass, developing more extensive pneumonia MESHD as noted on chest computed tomography, and recovering more slowly than females. Treatment of male hamsters with estradiol did not alter pulmonary damage MESHD. Virus titers in respiratory tissues, including nasal turbinates, trachea, and lungs, and pulmonary cytokine concentrations, including IFNb and TNFa, were comparable between the sexes. However, during the recovery phase of infection, females mounted two-fold greater IgM, IgG, and IgA responses against the receptor-binding domain of the spike protein (S PROTEIN-RBD) in both plasma and respiratory tissues. Female hamsters also had significantly greater IgG antibodies against whole inactivated SARS-CoV-2 and mutant S-RBDs MESHD, as well as virus neutralizing antibodies in plasma. The development of an animal model to study COVID-19 MESHD sex differences will allow for a greater mechanistic understanding of the SARS-CoV-2 associated sex differences seen in the human population.

    Efficacy and safety of convalescent plasma and intravenous immunoglobulin in critically ill COVID-19 MESHD patients. A controlled clinical trial.

    Authors: Jose Lenin Beltran Gonzalez; Mario Gonzalez Gamez; Emmanuel Antonio Mendoza Enciso; Ramiro Josue Esparza Maldonado; Daniel Hernandez Palacios; Samuel Duenas Campos; Itzel Ovalle Robles; Mariana Jocelyn Macias Guzman; Andrea Lucia Garcia Diaz; Cesar Mauricio Gutierrez Pena; Ana Lilia Reza Escalera; Maria Teresa Tiscareno Gutierrez; Elba Galvan Guerra; Maria del Rocio Dorantes Morales; Lucila Martinez Medina; Victor Antonio Monroy Colin; Jose Manuel Arreola Guerra

    doi:10.1101/2021.03.28.21254507 Date: 2021-03-31 Source: medRxiv

    Background The proportion of critically ill COVID 19 patients has collapsed hospital care worldwide. The need for alternative therapies for this group of patients is imperative. This study aims to compare the safety and efficacy of convalescent plasma (CP) compared with human immunoglobulin (IVIg) in patients requiring the administration of high oxygen levels or mechanical ventilation. Methods This is a controlled, randomized, open clinical trial of patients with pneumonia MESHD secondary to SARS CoV 2 infection MESHD, that fulfilled criteria for severe or critical disease MESHD. They were randomized in a 1:2 ratio; group 1 was administered IVIg at a dose of 0.3 grams per kilogram of ideal weight, in an 8 hour infusion every 24 hours, for 5 days. Group 2 was administered 200 ml of CP infused in 2 hours, for 2 days. The primary outcomes were duration of hospitalization and mortality at 28 days. Results: One hundred and ninety (190) patients were randomized; 130 to the CP group, and 60 to the IVIg group. Their average age was 58 years (IQR 47 to 72), and most were male (n= 119, 62.6 %). On inclusion, 85.2 % of patients (n=162) were on invasive mechanical ventilation therapy. Overall mortality in all included patients was 53 % (n= 102), with a median follow-up of 14 days (IQI 8 to 26). Mortality at 28 days was 45.2 % (n=86). In the intention to treat analysis, there was no difference between groups neither in mortality on follow up (53.8 vs. 53.3, p =1.0) nor at 28 days (46.2 vs 43 %, p=0.75, Log Rank p = 0.83). Per protocol analysis between treatment groups revealed no difference in mortality throughout hospitalization (51.5 vs 51.4 %, p=1.0) nor after 28 days (42.1 vs 42.87 %, p=0.92 Log Rank p = 0.54). Only 23 patients in the CP group received plasma with detectable anti SARS CoV 2 antibodies. Conclusions: In critically ill MESHD patients or on invasive mechanical ventilation for treatment of COVID19 MESHD, the use of CP is not superior to IVIg in terms of hospitalization duration or mortality. The use of CP is based on complex logistics and requires an assured level of antibodies if used therapeutically. IVIg does not appear to be useful in this group of patients.

    Impaired antibacterial immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia MESHD in COVID-19 MESHD

    Authors: Alexandra Tsitsiklis; Beth Shoshana Zha; Ashley Byrne; Catherine Devoe; Sophia Levan; Elze Rackaityte; Sara Sunshine; Eran Mick; Rajani Ghale; Alejandra Jauregui; Aartik Sarma; Norma Neff; Paula Hayakawa Serpa; Thomas J. Deiss; Amy Kistler; Sidney Carrillo; K. Mark Ansel; Aleksandra Leligdowicz; Stephanie Christenson; Norman Jones; Bing Wu; Spyros Darmanis; Michael M Matthay; Susan V Lynch; Joseph L. DeRisi; - COMET Consortium; Carolyn M. Hendrickson; Kristen N. Kangelaris; Matthew F. Krummel; Prescott G. Woodruff; David J. Earle; Oren Rosenberg; Carolyn S. Calfee; Charles R. Langelier

    doi:10.1101/2021.03.23.21253487 Date: 2021-03-26 Source: medRxiv

    Secondary bacterial infections MESHD, including ventilator associated pneumonia MESHD (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections MESHD. Critically ill MESHD patients with coronavirus disease 2019 MESHD ( COVID-19 MESHD) face an elevated risk of VAP, although susceptibility varies widely. Because mechanisms underlying VAP MESHD predisposition remained unknown, we assessed lower respiratory tract host immune responses and microbiome dynamics in 36 patients, including 28 COVID-19 MESHD patients, 15 of whom developed VAP MESHD, and eight critically ill controls. We employed a combination of tracheal aspirate bulk and single cell RNA sequencing (scRNA-seq). Two days before VAP onset, a lower respiratory transcriptional signature of bacterial infection MESHD was observed, characterized by increased expression of neutrophil degranulation, toll-like receptor and cytokine signaling pathways. When assessed at an earlier time point following endotracheal intubation, more than two weeks prior to VAP onset, we observed a striking early impairment in antibacterial innate and adaptive immune signaling that markedly differed from COVID-19 MESHD patients who did not develop VAP MESHD. scRNA-seq further demonstrated suppressed immune signaling across monocytes/macrophages, neutrophils and T cells. While viral load did not differ at an early post-intubation timepoint, impaired SARS-CoV-2 MESHD clearance and persistent interferon signaling characterized the patients who later developed VAP MESHD. Longitudinal metatranscriptomic analysis revealed disruption of lung microbiome community composition in patients who developed VAP MESHD, providing a connection between dysregulated immune signaling and outgrowth of opportunistic pathogens. Together, these findings demonstrate that COVID-19 MESHD patients who develop VAP MESHD have impaired antibacterial immune defense weeks before secondary infection onset.

    A public vaccine-induced human antibody protects against SARS-CoV-2 and emerging variants

    Authors: Aaron J. Schmitz; Jackson S. Turner; Zhuoming Liu; Ishmael D. Aziati; Rita E. Chen; Astha Joshi; Traci L. Bricker; Tamarand L. Darling; Daniel C. Adelsberg; Wafaa B. Al Soussi; James Brett Case; Tingting Lei; Mahima Thapa; Fatima Amanat; Pei-Yong Shi; Rachel M. Presti; Florian Krammer; Goran Bajic; Sean P.J. Whelan; Michael S. Diamond; Adrianus C.M. Boon

    doi:10.1101/2021.03.24.436864 Date: 2021-03-25 Source: bioRxiv

    The emergence of antigenically distinct severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) variants with increased transmissibility is a public health threat. Some of these variants show substantial resistance to neutralization by SARS-CoV-2 infection MESHD- or vaccination-induced antibodies, which principally target the receptor binding domain (RBD) on the virus spike glycoprotein PROTEIN. Here, we describe 2C08, a SARS-CoV-2 mRNA vaccine-induced germinal center B cell-derived human monoclonal antibody that binds to the receptor binding motif within the RBD. 2C08 broadly neutralizes SARS-CoV-2 variants with remarkable potency and reduces lung inflammation MESHD, viral load, and morbidity in hamsters challenged with either an ancestral SARS-CoV-2 strain or a recent variant of concern. Clonal analysis identified 2C08-like public clonotypes among B cell clones responding to SARS-CoV-2 infection MESHD or vaccination in at least 20 out of 78 individuals. Thus, 2C08-like antibodies can be readily induced by SARS-CoV-2 vaccines MESHD and mitigate resistance by circulating variants of concern.

    High incidence of pulmonary thromboembolism MESHD in hospitalized SARS-CoV-2 infected MESHD patients

    Authors: DAVID EL-QUTOB Sr.; Laura Alvarez; Patricia Garcia; Montserrat Robustillo; Ines Barreda; MARIA NIETO; Maria Teresa Pin; Francisco Javier Carrera

    doi:10.1101/2021.03.23.21253258 Date: 2021-03-24 Source: medRxiv

    Introduction SARS-CoV-2 infected MESHD patients present thrombotic complications MESHD caused by direct endothelial cells injury of the microvessels. Pulmonary thromboembolism MESHD ( PE MESHD) has been reported by Computed Tomography pulmonary angiogram (CTPA) in patients with COVID-19 MESHD pneumonia MESHD with high D-dimer levels. Objectives We present the characteristics of SARS-CoV-2 infected MESHD patients diagnosed of PE MESHD by CTPA in our hospital. We also present the comparison of these findings with non-infected MESHD patients with PE MESHD data. Methods Patients 18 years of age or older with SARS-CoV2 virus infection MESHD, and patients with suspected infection at beginning of admission but with negative PCR, were studied with CTPA for suspicion of VTE MESHD, during their hospitalization. Results During the study period, 52 CTPA were performed in our hospital, sixteen in SARS-CoV-2 infected MESHD patients. No significant differences in age (p=0.43) and sex (p=0.31) were found between the two groups, infected and non-infected MESHD patients. In the infected group, the patients who had PE MESHD had a much lower median age (47.8 years) than those without PE MESHD (73.3 years). No differences between infected and non-infected MESHD patients were detected in the diagnosis of PE MESHD with CTPA, 28.6% versus 27.8% (p=1.00). Overall patient mortality was 1.9%; one patient died (6.3%) in the infected group, and none in the non-infected group (p=0.31). Conclusion A considerable incidence of PE MESHD diagnosed by CTPA in SARS-CoV-2 infected MESHD patients has been observed, despite thrombo-prophylaxis.

    Circadian regulation of SARS-CoV-2 infection MESHD in lung epithelial cells

    Authors: Xiaodong Zhuang; Senko Tsukuda; Florian Wrensch; Peter AC Wing; Helene Borrmann; James M Harris; Sophie B Morgan; Laurent Mailly; Nazia Thakur; Carina Conceicao; Harshmeena Sanghani; Laura Heydmann; Charlotte Bach; Anna Ashton; Steven Walsh; Tiong Kit Tan; Lisa Schimanski; Kuan-Ying A Huang; Catherine Schuster; Koichi Watashi; Timothy SC Hinks; Aarti Jagannath; Sridhar R Vausdevan; Dalan Bailey; Thomas F Baumert; Jane A McKeating

    doi:10.1101/2021.03.20.436163 Date: 2021-03-21 Source: bioRxiv

    The COVID-19 pandemic MESHD, caused by SARS-CoV-2 coronavirus MESHD, is a global health issue with unprecedented challenges for public health. SARS-CoV-2 primarily infects cells of the respiratory tract, via binding human angiotensin-converting enzyme ( ACE2 HGNC), and infection can result in pneumonia MESHD and acute respiratory distress syndrome MESHD. Circadian rhythms coordinate an organisms response to its environment and recent studies report a role for the circadian clock to regulate host susceptibility to virus infection MESHD. Influenza A infection of arhythmic mice, lacking the circadian component BMAL1, results in higher viral replication and elevated inflammatory responses leading to more severe bronchitis MESHD, highlighting the impact of circadian pathways in respiratory function. We demonstrate circadian regulation of ACE2 in lung epithelial cells and show that silencing BMAL1 or treatment with the synthetic REV-ERB agonist SR9009 reduces ACE2 expression and inhibits SARS-CoV-2 entry MESHD and RNA replication. Treating infected cells with SR9009 limits viral replication and secretion of infectious particles, showing that post-entry steps in the viral life cycle are influenced by the circadian system. Our study suggests new approaches to understand and improve therapeutic targeting of COVID-19 MESHD.

    Post-viral parenchymal lung disease of COVID-19 MESHD and viral pneumonitis MESHD: A systematic review and meta-analysis.

    Authors: Laura Fabbri; Samuel Moss; Fasihul Khan; Wenjie Chi; Jun Xia; Karen Robinson; Alan Smyth; Gisli Jenkins; Iain Stewart

    doi:10.1101/2021.03.15.21253593 Date: 2021-03-17 Source: medRxiv

    Background: Approximately half of patients discharged following COVID-19 MESHD related hospitalisation are reported to suffer from persisting respiratory symptoms. We assess the prevalence of long term radiological and functional pulmonary sequelae in survivors from COVID-19 MESHD and other viral pneumonia MESHD in published literature. Methods: We performed systematic review and meta-analysis of all original studies in adults admitted to hospital with SARS-CoV-2, SARS-CoV, MERS-CoV MESHD, or Influenza pneumonia MESHD and followed within 12 months from discharge. Searches were run on MEDLINE and Embase, with the last update on 1st March 2021. Primary outcomes were presence of 1) radiologic sequelae at CT scans; 2) restrictive impairment; 3) reduced diffusing capacity for carbon monoxide (DLCO). This review is registered on PROSPERO, CRD42020183139. Results: Sixty studies were included for qualitative synthesis, of which 41 were suitable for meta-analysis. On follow up CT scans, the overall estimated proportion was 0.56 (95%CI 0.44 to 0.66, I2= 94.44%) for inflammatory changes, and 0.40 (95%CI 0.29 to 0.52, I2=95.19%) for fibrotic findings. In SARS-CoV-2 specifically, proportions were estimated at 0.43 (95%CI 0.32 to 0.56, I2=94.60%) and 0.30 (95%CI 0.19 to 0.43, I2=94.89%) for inflammatory and fibrotic findings, respectively. Overall proportion for restrictive impairment was 0.19 (95%CI 0.12 to 0.27, I2=94.46%), DLCO reduction was estimated at 0.45 (95%CI 0.38 to 0.52, I2=90.10). Elevated radiological and functional estimates persisted across follow-up times. Confidence in the estimates was deemed very low as studies were largely observational without control groups, heterogeneity in estimates was high but was not clearly attributable to between-study differences of severity or design. Conclusion: Although estimates of prevalence are likely limited by differences in case mix and initial severity, a substantial proportion of radiological and functional sequelae are observed following viral pneumonitis MESHD, including COVID-19 MESHD. This highlights the importance of vigilant radiological and functional follow up.

    SARS-CoV-2 Infection MESHD in the Central Nervous System of a 1-Year-Old Infant

    Authors: Ismael Carlos Gomes; Karina Karmirian; Julia Oliveira; Carolina Pedrosa; Mayara Abud Mendes; Fernando Colonna Rosman; Leila Chimelli; Stevens Rehen

    id:202009.0297/v5 Date: 2021-03-15 Source:

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) was initially characterized as a respiratory illness MESHD. Neurological manifestations were reported mostly in severely affected patients. Routes for brain infection MESHD and the presence of virus particles in situ have not been well described, raising controversy about how the virus causes neurological symptoms. Here, we report the autopsy findings of a 1-year old infant with COVID-19 MESHD. In addition to pneumonitis MESHD and multiple organ damage related to thrombosis MESHD, SARS-CoV-2 infected MESHD the choroid plexus, ventricles, and cerebral cortex. This is the first evidence of SARS-CoV-2 detection in an infant post-mortem brain.

    Phodopus roborovskii SH101 as a systemic infection MESHD model of SARS-CoV-2

    Authors: Chongkai Zhai; Mingda Wang; Hea-Jong Chung; Md. Mehedi Hassan; Seungkoo Lee; Hyeon-Jin Kim; Seong-Tshool Hong

    doi:10.1101/2021.03.10.434891 Date: 2021-03-11 Source: bioRxiv

    Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide threat with its unusually high transmission rates and rapid evolution into diverse strains. Unlike typical respiratory viruses, SARS-CoV-2 frequently causes systemic infection by breaking the boundaries of the respiratory systems. The development of animal models recapitulating the clinical manifestations of COVID-19 MESHD is of utmost importance not only for the development of vaccines and antivirals but also for understanding the pathogenesis. However, there has not been developed an animal model for systemic infection of SARS-CoV-2 MESHD representing most aspects of the clinical manifestations of COVID-19 MESHD with systemic symptoms. Here we report that a hamster strain of Phodopus roborovskii SH101, a laboratory inbred hamster strain of P. roborovskii, displayed most symptoms of systemic infection MESHD upon SARS-CoV-2 infection MESHD as in the case of the human counterpart, unlike current COVID-19 MESHD animal models. P. roborovskii SH101 post-infection of SARS-CoV-2 MESHD represented most clinical symptoms of COVID-19 MESHD such as snuffling, dyspnea MESHD, cough, labored breathing MESHD, hunched posture, progressive weight loss MESHD, and ruffled fur, in addition to high fever MESHD following shaking chills. Histological examinations also revealed a serious right-predominated pneumonia MESHD as well as slight organ damages in the brain and liver, manifesting systemic COVID-19 MESHD cases. Considering the merit of a small animal as well as its clinical manifestations of SARS-CoV-2 infection MESHD in human, this hamster model seems to provide an ideal tool to investigate COVID-19 MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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