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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

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    Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike PROTEIN variants

    Authors: Satoshi Ikegame; Mohammed N. A. Siddiquey; Chuan-Tien Hung; Griffin Haas; Luca Brambilla; Kasopefoluwa Y. Oguntuyo; Shreyas Kowdle; Ariel Esteban Vilardo; Alexis Edelstein; Claudia Perandones; Jeremy P. Kamil; Benhur Lee

    doi:10.1101/2021.03.31.21254660 Date: 2021-04-02 Source: medRxiv

    The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia MESHD outbreak in Wuhan, China. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 variants of concern (VOC) across diverse geographic locales suggests herd immunity may fail to eliminate the virus. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus MESHD ( VSV MESHD) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV MESHD-G, coupled with a clonal HEK-293T ACE2 HGNC TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that 8 out of 12 (75%) of serum samples from 12 recipients of the Russian Sputnik V Ad26 / Ad5 vaccine showed dose response curve slopes indicative of failure to neutralize rcVSV-CoV2-S: B.1.351. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of emergent SARS-CoV-2 variants may benefit from updated vaccines.

    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.

    Cyclooxgenase-2 is induced by SARS-CoV-2 infection MESHD but does not affect viral entry or replication

    Authors: Jennifer S. Chen; Mia Madel Alfajaro; Jin Wei; Ryan D. Chow; Renata B Filler; Stephanie C. Eisenbarth; Craig B Wilen; Li Hui Tan; Beihua Dong; Konstantinos Dionysios Alysandratose; Jesse Huang; James N Palmer; Nithin D Adappa; Michael A Kohanski; Darrell N Kotton; Robert H Silverman; Wenli Yang; Edward Morrisey; Noam Cohen; Susan R Weiss; David C. Jackson; Nathan W Bartlett; Francesca Mercuri; Miles W Carroll; Sonam T. Nyatsatsang; Alexander L. Greninger; Ansuman T. Satpathy; John S Pauk; Scott D. Boyd; James R. Heath

    doi:10.1101/2020.09.24.312769 Date: 2020-09-25 Source: bioRxiv

    Identifying drugs that regulate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD and its symptoms has been a pressing area of investigation during the coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic. Nonsteroidal anti-inflammatory drugs (NSAIDs), which are frequently used for the relief of pain MESHD and inflammation MESHD, could modulate both SARS-CoV-2 infection MESHD and the host response to the virus. NSAIDs inhibit the enzymes cyclooxygenase-1 HGNC ( COX-1 HGNC) and cyclooxygenase-2 HGNC ( COX-2 HGNC), which mediate the production of prostaglandins (PGs). PGE2, one of the most abundant PGs, has diverse biological roles in homeostasis and inflammatory responses. Previous studies have shown that NSAID treatment or inhibition of PGE2 receptor signaling leads to upregulation of angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC), the cell entry receptor for SARS-CoV-2, thus raising concerns that NSAIDs could increase susceptibility to infection. COX/PGE2 signaling has also been shown to regulate the replication of many viruses, but it is not yet known whether it plays a role in SARS-CoV-2 replication. The purpose of this study was to dissect the effect of NSAIDs on COVID-19 MESHD in terms of SARS-CoV-2 entry MESHD and replication. We found that SARS-CoV-2 infection MESHD induced COX-2 HGNC upregulation in diverse human cell culture and mouse systems. However, suppression of COX-2/PGE2 signaling by two commonly used NSAIDs, ibuprofen and meloxicam, had no effect on ACE2 HGNC expression, viral entry, or viral replication. Our findings suggest that COX-2 HGNC signaling driven by SARS-CoV-2 may instead play a role in regulating the lung inflammation MESHD and injury observed in COVID-19 MESHD patients.

    Modeling COVID-19 MESHD with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 HGNC Inhibition Against SARS-CoV-2

    Authors: Fuyu Duan; Liyan Guo; Liuliu Yang; Yuling Han; Abhimanyu Thakur; Benjamin E. Nilsson-Payant; Pengfei Wang; Zhao Zhang; Chui Yan Ma; Xiaoya Zhou; Teng Han; Tuo Zhang; Xing Wang; Dong Xu; Xiaohua Duan; Jenny Xiang; Hung-fat Tse; Can Liao; Weiren Luo; Fang-Ping Huang; Ya-Wen Chen; Todd Evans; Robert E. Schwartz; Benjamin tenOever; David D. Ho; Shuibing Chen; Jie Na; Qizhou Lian; Huanhuan Joyce Chen

    doi:10.21203/rs.3.rs-62758/v2 Date: 2020-08-20 Source: ResearchSquare

    Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease MESHD-2019 ( COVID-19 MESHD) from mild to severe stages including fatality, with pro-inflammatory macrophages as one of the main mediators of lung hyper-inflammation MESHD. Therefore, there is an urgent need to better understand the interactions among SARS-CoV-2 permissive cells, macrophage, and the SARS-CoV-2 virus, thereby offering important insights into new therapeutic strategies.  Here, we used directed differentiation of human pluripotent stem cells (hPSCs) to establish a lung and macrophage co-culture system and model the host-pathogen interaction and immune response caused by SARS-CoV-2 infection MESHD. Among the hPSC-derived lung cells, alveolar type II MESHD and ciliated cells are the major cell populations expressing the viral receptor ACE2 HGNC and co-effector TMPRSS2 HGNC, and both were highly permissive to viral infection MESHD. We found that alternatively polarized macrophages (M2) and classically polarized macrophages (M1) had similar inhibitory effects on SARS-CoV-2 infection MESHD. However, only M1 macrophages significantly up-regulated inflammatory factors including IL-6 HGNC and IL-18 HGNC, inhibiting growth and enhancing apoptosis of lung cells. Inhibiting viral entry into target cells using an ACE2 HGNC blocking antibody enhanced the activity of M2 macrophages, resulting in nearly complete clearance of virus and protection of lung cells. These results suggest a potential therapeutic strategy, in that by blocking viral entrance to target cells while boosting anti-inflammatory action of macrophages at an early stage of infection, M2 macrophages can eliminate SARS-CoV-2, while sparing lung cells and suppressing the dysfunctional hyper MESHD-inflammatory response mediated by M1 macrophages.    

    A blood-based comprehensive and systems-level analysis of disease stages, immune regulation and symptoms in COVID-19 MESHD patients

    Authors: Anguraj Sadanandam; Tobias Bopp; Santosh Dixit; David JHF Knapp; Chitra Priya Emperumal; Krishnaraj Rajalingam; Alan Melcher; Nagarajan Kannan

    doi:10.21203/rs.3.rs-30473/v1 Date: 2020-05-20 Source: ResearchSquare

    COVID-19 MESHD patients show significant clinical heterogeneity in presentation and outcomes that makes pandemic control and strategy difficult; optimising management requires a systems biology approach of understanding the disease. Here we sought to understand and infer complex system-wide changes in patients infected with coronaviruses ( SARS-CoV and SARS-CoV-2 MESHD; n=38 and 57 samples) at two different disease stages compared with healthy individuals (n=16) and patients with other infections (n=144). We applied inferential statistics/machine-learning approaches (the COVID-engine platform) to RNA profiles derived from peripheral blood mononuclear cells (PBMCs). Compared to healthy individuals, an integrated blood-based gene signatures distinguished acute-like (mimicking coronavirus-infected MESHD patients with prolonged hospitalisation) from recovering-like patients. These signatures also hierarchically represented systems-level parameters associated with PBMC including dysregulated cytokines, genes, pathways, networks of pathways/concepts, immune status, and cell types. Proof-of-principle confirmatory observations included PBMC-associated increases in ACE2 HGNC, cytokine storm-associated IL6 HGNC, enhanced innate immunity (macrophages and neutrophils), and lower adaptive T and B cell immunity in patients with acute-like disease compared to those with recovery-like disease. Patients in the recovery-like stage had significantly enhanced TNF HGNC, IFN-g HGNC, anti-viral, HLA-DQA1 HGNC, and HLA-F HGNC gene expression and cytolytic activity, and reduced pro-viral gene expression compared to those in the acute-like stage in PBMC. Besides, PBMC-derived surrogate-based approach revealed overlapping genes associated with comorbidities (associated diabetes MESHD), and disease-like symptoms (associated with thromboembolism MESHD, pneumonia MESHD, lung disease MESHD and septicaemia MESHD). Overall, our study involving PBMC-based RNA profiling may further help understand complex and variable systems-wide responses displayed by coronavirus-infected MESHD patients.

    Novel ACE2 HGNC-Independent Carbohydrate-Binding of SARS-CoV-2 Spike PROTEIN Protein to Host Lectins and Lung Microbiota

    Authors: Fabrizio Chiodo; Sven C.M Bruijns; Ernesto Rodriguez; R.J. Eveline Li; Antonio Molinaro; Alba Silipo; Flaviana Di Lorenzo; Dagmar Garcia-Rivera; Yury Valdes-Balbin; Vicente Verez-Bencomo; Yvette van Kooyk

    doi:10.1101/2020.05.13.092478 Date: 2020-05-14 Source: bioRxiv

    The immediate call for translational research in the field of coronavirus disease MESHD ( COVID-19 MESHD) pandemic, needs new and unexplored angles to support and contribute to this important worldwide health problem. The aim of this study is to better understand the pathogenic mechanisms underlying COVID-19 MESHD, deciphering the carbohydrate-mediated interactions of the SARS-CoV-2 spike PROTEIN protein. We studied the carbohydrate-binding receptors that could be important for viral entry and for immune-modulatory responses, and we studied the interactions of the spike protein PROTEIN with the host lung microbiota. Exploring solid-phase immunoassays, we evaluated the interactions between the SARS-CoV-2 spike PROTEIN protein and a library of 12 different human carbohydrate-binding proteins (C-type lectins and Siglecs) involved in binding, triggering and modulation of innate and adaptive immune-responses. We revealed a specific binding of the SARS-CoV-2 spike PROTEIN protein to the receptors DC-SIGN, MGL HGNC, Siglec-9 HGNC and Siglec-10 HGNC that are all expressed on myeloid immune cells. In addition, because the lung microbiota can promote or modulate viral infection, we studied the interactions between the SARS-CoV-2 spike PROTEIN protein and a library of Streptococcus pneumoniae capsular polysaccharides, as well as other bacterial glyco-conjugates. We show specific binding of the spike protein PROTEIN to different S. pneumoniae capsular polysaccharides (serotypes 19F and 23F but not to serotype 14). Moreover we demonstrated a specific binding of SARS-CoV-2 spike PROTEIN protein to the lipopolysaccharide from the opportunistic human pathogen Pseudomonas aeruginosa, one of the leading cause of acute nosocomial infections MESHD and pneumonia MESHD. Interestingly, we identified rhamnosylated epitopes as one of the discriminating structures in lung microbiota to bind SARS-CoV-2 spike PROTEIN protein. In conclusion, we revealed novel ACE2 HGNC-independent carbohydrate-mediated interactions with immune modulating lectins expressed on myeloid cells, as well as host lung microbiota glyco-conjugates. Our results identified new molecular pathways using host lectins and signalling, that may contribute to viral infection MESHD and subsequent immune exacerbation. Moreover we identified specific rhamnosylated epitopes in lung microbiota to bind SARS-CoV-2, providing a hypothetical link between the presence of specific lung microbiota and SARS-CoV-2 infection MESHD and severity.

    Ultra-fast and onsite interrogation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in environmental specimens via surface enhanced Raman scattering ( SERS HGNC)

    Authors: Dayi Zhang; Xiaoling Zhang; Rui Ma; Songqiang Deng; Xinquan Wang; Xian Zhang; Xia Huang; Yi Liu; Guanghe Li; Jiuhui Qu; Yu Zhu; Junyi Li

    doi:10.1101/2020.05.02.20086876 Date: 2020-05-06 Source: medRxiv

    The outbreak of coronavirus infectious disease MESHD-2019 ( COVID-19 MESHD) pneumonia MESHD challenges the rapid interrogation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human and environmental specimens. In this study, we developed an assay using surface enhanced Raman scattering ( SERS HGNC) coupled with multivariate analysis to diagnose SARS-CoV-2 in an ultra-fast manner without any pretreatment (e.g., RNA extraction). Using silver-nanorod SERS HGNC array functionalized with cellular receptor angiotensin-converting enzyme 2 ( ACE2 HGNC), we obtained strong SERS HGNC signals of ACE2 HGNC at 1032, 1051, 1089, 1189, 1447 and 1527 cm-1. The recognition and binding of receptor binding domain (RBD) of SARS-CoV-2 spike PROTEIN protein on SERS HGNC assay significantly quenched the spectral intensities of most peaks and exhibited a shift from 1189 to 1182 cm-1. On-site tests on 17 water samples with a portable Raman spectrometer proved its accuracy and easy-operation for spot diagnosis of SARS-CoV-2 to evaluate disinfection performance, explore viral survival in environmental media, assess viral decay in wastewater treatment plant and track SARS-CoV-2 in pipe network. Our findings raise a state-of-the-art spectroscopic tool to screen and interrogate viruses with RBD for human cell entry, proving its feasibility and potential as an ultra-fast diagnostic tool for public health.

    SARS-CoV-2 mortality in blacks and temperature-sensitivity to an angiotensin-2 receptor blocker

    Authors: Donald R. Forsdyke

    id:2005.01579v5 Date: 2020-04-30 Source: arXiv

    Tropical climates provoke adaptations in skin pigmentation MESHD and in mechanisms controlling the volume, salt-content and pressure of body fluids. For many whose distant ancestors moved to temperate climes, these adaptations proved harmful: pigmentation decreased by natural selection and susceptibility to hypertension MESHD emerged. Now an added risk is lung inflammation MESHD from coronavirus that may be furthered by innate immune differences. Hypertension MESHD and coronavirus have in common angiotensin converting enzyme 2 HGNC ( ACE2 HGNC), which decreases blood pressure and mediates virus entry. In keeping with less detailed studies, a long-term case-report shows that decreased blood pressure induced by blocking a primary angiotensin receptor is supplemented, above critical blocker dosage, by a further temperature-dependent fall, likely mediated by ACE2 HGNC and secondary angiotensin receptors. Temperature-dependence suggests a linkage with tropical heritage and an influence of blockers on the progress of coronavirus infections MESHD. Positive therapeutic results should result from negation of host pro-inflammatory effects mediated by the primary angiotensin receptor and concomitant promotion of countervailing anti-inflammatory effects mediated by ACE2 HGNC through other receptors. These effects may involve innate immune system components (lectin complement pathway, NAD metabolome). Black vulnerability - more likely based on physiological than on socioeconomic differences - provides an important clue that may guide treatments.

    Neuroinvasive Potential of A Primary Respiratory Pathogen SARS-CoV2: Exploring the Underrecognized

    Authors: Durjoy Lahiri; Ritwick Mondal; Shramana Deb; Deebya Bandopadhyay; Gourav Shome; Sukanya Sarkar; Subhas C. Biswas

    id:10.20944/preprints202004.0382.v1 Date: 2020-04-21 Source: Preprints.org

    After the emergence of Severe Acute Respiratory Syndrome Coronavirus(SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV MESHD) in the last two decades, the world is facing its new challenge in SARS-CoV-2 pandemic with unfathomable global responses. The characteristic clinical symptoms for Coronavirus ( COVID-19 MESHD) affected patients are high fever, dry-cough, dyspnoea MESHD, lethal pneumonia MESHD whereas some patients also show few additional neurological signs such as headache MESHD, nausea MESHD, vomiting MESHD. The accumulative evidences suggest that Coronavirus is not only confined within the respiratory tract and that may also invade in central nervous system (CNS), peripheral nervous system (PNS) inducing some fatal Neurological diseases MESHD. Here we analyse the phylogenetic perspective of SARS-CoV2 with other strains of β-Coronaviridae from a standpoint of neurological spectrum disorders MESHD. Based on the existing case reports, literature and open data-bases, we also analyse the differential distribution of neurological impairments MESHD in COVID-19 MESHD positive patients along with angiotensin-converting enzyme-2 HGNC( ACE2 HGNC) expression dynamics in neuronal and non-neuronal tissue of central and peripheral nervous system. Besides, we discuss the need for modulations in clinical approach from a neurological point of view, as a measure towards reducing disease transmission, morbidity and mortality in SARS-CoV2 positive patients.

    The Pathophysiology of Virulence of the COVID-19 MESHD

    Authors: Joseph De Soto; Shazia Hakim; Frederick Boyd

    id:10.20944/preprints202004.0077.v2 Date: 2020-04-15 Source: Preprints.org

    Background: On Dec 19, 2019, the public health department of China reported that an outbreak of pneumonia MESHD was caused by a novel Coronavirus. The virulence of the new virus COVID-19 MESHD was much greater than either the SARs and MERSs viruses and on March 11, 2020, the World Health Department (WHO) declared a worldwide pandemic. Understanding the pathophysiology of virulence of the SARS-COV-2 virus is absolutely necessary for understanding the transmission, virulence factors, reduce risk factors, clinical presentation, predict outcomes of the disease and provide guidance for any current or future treatment protocols. Methodology: A comprehensive PubMed search was performed during December 20, 2019 and April 03, 2020, utilizing the words: Wuhan Virus, COVID-19 MESHD, SARs coronavirus MESHD, ACE2, S-protein PROTEIN, virulence, clinical presentation, epidemiology, genome, treatment, structure, MERs, pathogenesis and/or pathology alone and in combination with other terms. Each paper was evaluated by three content experts for quality, reproducibility, credibility and reputation of the journal. Results: The SARS-COV-2 virus is much more virulent than either the SAR’s or MER’s virus and its ability to cause serious disease inversely corresponds to the person’s ability to produce T-cells which declines linearly with age. The ACE2 receptor binding site does not vary among different ethnic groups but do in ACE-2 HGNC expression levels. This variance in expression level may explain for different infectivity rates among men and women and predict and explain different susceptibilities to infection by different ethnic groups. Furthermore, by understanding the underlying pathophysiology one can explain and provide guidance to the clinical effectiveness of any treatment. Conclusions: The underlying pathophysiology of COVID-19 MESHD explains not only the virulence, and clinical presentation, but, explains at a molecular level the comorbidity risk factors such as hypertension MESHD, sex, and age. Ethnic and anatomic expression patterns of ACE-2 HGNC and associated pathophysiology suggests that Native Americans and Asians may be particularly susceptible to this disease.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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