Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (99)

NSP5 (7)

ProteinN (4)

ComplexRdRp (4)

ProteinE (2)


SARS-CoV-2 Proteins
    displaying 11 - 20 records in total 184
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    Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways

    Authors: Ke Xu; Xingyi Shi; Chris Husted; Rui Hong; Yichen Wang; Boting Ning; Travis Sullivan; Kimberly M Rieger-Christ; Fenghai Duan; Helga Marques; Adam C Gower; Xiaohui Xiao; Hanqiao Liu; Gang Liu; Grant Duclos; Avrum Spira; Sarah A Mazzilli; Ehab Billatos; Marc E Lenburg; Joshua D Campbell; Jennifer Beane

    doi:10.1101/2021.03.30.21254564 Date: 2021-04-04 Source: medRxiv

    Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) is caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), which infects host cells with help from the Viral Entry (VE) proteins ACE2 HGNC, TMPRSS2 HGNC, and CTSL HGNC. Proposed risk factors for viral infection MESHD, as well as the rate of disease progression, include age, sex, chronic obstructive pulmonary disease MESHD, cancer MESHD, and cigarette smoking. To investigate whether the proposed risk factors increase viral infection MESHD by modulation of the VE genes, we examined gene expression profiles of 796 nasal and 1,673 bronchial samples across four lung cancer MESHD screening cohorts containing individuals without COVID-19 MESHD. Smoking was the only clinical factor reproducibly associated with the expression of any VE gene across cohorts. ACE2 HGNC expression was significantly up-regulated with smoking in the bronchus but significantly down-regulated with smoking in the nose. Furthermore, expression of individual VE genes were not correlated between paired nasal and bronchial samples from the same patients. Single-cell RNA-seq of nasal brushings revealed that an ACE2 HGNC gene module was detected in a variety of nasal secretory cells with the highest expression in the C15orf48 HGNC+ secretory cells, while a TMPRSS2 HGNC gene module was most highly expressed in nasal keratinizing epithelial cells. In contrast, single-cell RNA-seq of bronchial brushings revealed that ACE2 HGNC and TMPRSS2 HGNC gene modules were most enriched in MUC5AC HGNC+ bronchial goblet cells. The CTSL HGNC gene module was highly expressed in immune populations of both nasal and bronchial brushings. Deconvolution of bulk RNA-seq showed that the proportion of MUC5AC HGNC+ goblet cells was increased in current smokers in both the nose and bronchus but proportions of nasal keratinizing epithelial cells, C15orf48 HGNC+ secretory cells, and immune cells were not associated with smoking status. The complex association between VE gene expression and smoking in the nasal and bronchial epithelium revealed by our results may partially explain conflicting reports on the association between smoking and SARS-CoV-2 infection MESHD.

    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.

    Sulforaphane exhibits in vitro and in vivo antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses MESHD

    Authors: Alvaro A Ordonez; Cynthia K Bullen; Andres F Villabona-Rueda; Elizabeth A Thompson; Mitchell L Turner; Stephanie L Davis; Oliver Komm; Jonathan D Powell; Robert H Yolken; Sanjay K Jain; Lorraine Jones-Brando

    doi:10.1101/2021.03.25.437060 Date: 2021-03-25 Source: bioRxiv

    Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 MESHD ( COVID-19 MESHD), has incited a global health crisis. Currently, there are no orally available medications for prophylaxis for those exposed to SARS-CoV-2 and limited therapeutic options for those who develop COVID-19 MESHD. We evaluated the antiviral activity of sulforaphane ( SFN HGNC), a naturally occurring, orally available, well-tolerated, nutritional supplement present in high concentrations in cruciferous vegetables with limited side effects. SFN inhibited in vitro replication of four strains of SARS-CoV-2 as well as that of the seasonal coronavirus HCoV-OC43. Further, SFN and remdesivir interacted synergistically to inhibit coronavirus infection MESHD in vitro. Prophylactic administration of SFN to K18- hACE2 HGNC mice prior to intranasal SARS-CoV-2 infection MESHD significantly decreased the viral load in the lungs and upper respiratory tract and reduced lung injury MESHD and pulmonary pathology compared to untreated infected mice. SFN treatment diminished immune cell activation in the lungs, including significantly lower recruitment of myeloid cells and a reduction in T cell activation and cytokine production. Our results suggest that SFN is a promising treatment for prevention of coronavirus infection MESHD or treatment of early disease.

    CVnCoV protects human ACE2 HGNC transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2

    Authors: Donata Hoffmann; Bjoern Corleis; Susanne Rauch; Nicole Roth; Janine Muehe; Nico Joel Halwe; Lorenz Ulrich; Charlie Fricke; Jacob Schoen; Anna Kraft; Angele Breithaupt; Kerstin Wernike; Anna Michelitsch; Franziska Sick; Claudia Wylezich; Stefan O. Mueller; Thomas C. Mettenleiter; Benjamin Petsch; Anca Dorhoi; Martin Beer

    doi:10.1101/2021.03.22.435960 Date: 2021-03-22 Source: bioRxiv

    The ongoing severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) pandemic necessitates the fast development of vaccines as the primary control option. Recently, viral mutants termed "variants of concern" (VOC) have emerged with the potential to escape host immunity. VOC B.1.351 was first discovered in South Africa in late 2020, and causes global concern due to poor neutralization with propensity to evade preexisting immunity from ancestral strains. We tested the efficacy of a spike encoding mRNA vaccine (CVnCoV) against the ancestral strain BavPat1 and the novel VOC B.1.351 in a K18- hACE2 HGNC transgenic mouse model. Naive mice and mice immunized with formalin-inactivated SARS-CoV-2 preparation were used as controls. mRNA-immunized mice developed elevated SARS-CoV-2 RBD-specific antibody as well as neutralization titers against the ancestral strain BavPat1. Neutralization titers against VOC B.1.351 were readily detectable but significantly reduced compared to BavPat1. VOC B.1.351-infected control animals experienced a delayed course of disease, yet nearly all SARS-CoV-2 challenged naive mice succumbed with virus dissemination and high viral loads. CVnCoV vaccine completely protected the animals from disease and mortality caused by either viral strain. Moreover, SARS-CoV-2 was not detected in oral swabs, lung, or brain in these groups. Only partial protection was observed in mice receiving the formalin-inactivated virus preparation. Despite lower neutralizing antibody titers compared to the ancestral strain BavPat1, CVnCoV shows complete disease protection against the novel VOC B.1.351 in our studies.

    A bispecific monomeric nanobody induces SARS-COV-2 spike trimer dimers

    Authors: Leo Hanke; Hrishikesh Das; Daniel Sheward; Laura Perez Vidakovics; Egon Urgard; Ainhoa Moliner Morro; Vivien Karl; Alec Pankow; Kim Changil; Natalie Smith; Gabriel Pedersen; Jonathan M Coquet; B Martin Hallberg; Benjamin Murrell; Gerald M McInerney

    doi:10.1101/2021.03.20.436243 Date: 2021-03-21 Source: bioRxiv

    Antibodies binding to the severe acute respiratory syndrome coronavirus 2 MESHD ( SARS-CoV-2) spike PROTEIN have therapeutic promise, but emerging variants show the potential for virus escape. Thus, there is a need for therapeutic molecules with distinct and novel neutralization mechanisms. Here we isolated a nanobody that potently neutralizes SARS-CoV-2, including the B.1.351 variant, and cross-neutralizes SARS-CoV MESHD. We demonstrate the therapeutic potential of the nanobody in a human ACE2 HGNC transgenic mouse model. Using biochemistry and electron cryomicroscopy we show that this nanobody simultaneously interacts with two RBDs from different spike trimers, rapidly inducing the formation of spike trimer-dimers. This naturally elicited bispecific monomeric nanobody establishes a novel strategy for potent immobilization of viral antigens.

    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.

    3D genomic capture of regulatory immuno-genetic profiles in COVID-19 MESHD patients for prognosis of severe COVID disease outcome MESHD

    Authors: Ewan Hunter; Christina Koutsothanasi; Adam Wilson; Francisco Coroado Santos; Matthew Salter; Ryan Powell; Ann Dring; Paulina Brajer; Benedict Egan; Jurjen Westra; Aroul Ramadass; William Messner; Amanda Brunton; Zoe Lyski; Rama Vancheeswaran; Andrew Barlow; Dmitri Pchejetski; Alexandre Akoulitchev

    doi:10.1101/2021.03.14.435295 Date: 2021-03-16 Source: bioRxiv

    Human infection with the SARS-CoV-2 virus leads to coronavirus disease MESHD ( COVID-19 MESHD). A striking characteristic of COVID-19 MESHD infection in humans is the highly variable host response and the diverse clinical outcomes, ranging from clinically asymptomatic to severe immune reactions leading to hospitalization and death MESHD. Here we used a 3D genomic approach to analyse blood samples at the time of COVID diagnosis, from a global cohort of 80 COVID-19 MESHD patients, with different degrees of clinical disease outcomes. Using 3D whole genome EpiSwitch(R) arrays to generate over 1 million data points per patient, we identified a distinct and measurable set of differences in genomic organization at immune-related loci that demonstrated prognostic power at baseline to stratify patients with mild forms of illness and those with severe forms that required hospitalization and intensive care unit (ICU) support. Further analysis revealed both well established and new COVID-related dysregulated pathways and loci, including innate and adaptive immunity; ACE2 HGNC; olfactory, G{beta}{psi}, Ca2+ and nitric oxide (NO) signalling; prostaglandin E2 (PGE2), the acute inflammatory cytokine CCL3 HGNC, and the T-cell derived chemotactic cytokine CCL5 HGNC. We identified potential therapeutic agents for mitigation of severe disease outcome, with several already being tested independently, including mTOR HGNC inhibitors (rapamycin and tacrolimus) and general immunosuppressants (dexamethasone and hydrocortisone). Machine learning algorithms based on established EpiSwitch(R) methodology further identified a subset of 3D genomic changes that could be used as prognostic molecular biomarker leads for the development of a COVID-19 MESHD disease severity test.

    Differential gene expression by RNA-Seq in Sigma-2 Receptor/ TMEM97 HGNC knockout cells reveals its role in complement activation and SARS-CoV-2 viral uptake


    doi:10.1101/2021.03.14.435180 Date: 2021-03-15 Source: bioRxiv

    Our lab has recently shown that the Sigma-2 Receptor/Transmembrane Protein 97 (sigma- 2R/ TMEM97 HGNC) interacts with the low-density lipoprotein receptor HGNC ( LDLR HGNC) and facilitates the enhanced uptake of various ligands including lipoproteins and intrinsically disordered proteins. TMEM97 HGNC has been recently been shown to interact with severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) viral proteins, highlighting its potential involvement with viral entry into the cell. We hypothesized that sigma-2R/ TMEM97 HGNC may play a role in facilitating viral uptake, and with the regulation of inflammatory and thrombotic MESHD pathways that are involved with viral infection MESHD. In this study, we identified the top differentially expressed genes upon the knockout of sigma-2R/ TMEM97 HGNC, and analyzed the genes involved with the inflammatory and thrombotic MESHD cascades, effects that are observed in patients infected with SARS-CoV-2. We found that the ablation of sigma-2R/ TMEM97 HGNC resulted in an increase in Complement Component MESHD 4 Binding Protein ( C4BP HGNC) proteins, at both the translational and transcriptional levels. We also showed that sigma-2R/ TMEM97 HGNC interacts with the cellular receptor for SARS-CoV-2, the human angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) receptor, forming a protein complex, and that disruption of this complex results in the inhibition of viral uptake. The results of this study suggest that sigma-2R/ TMEM97 HGNC may be a novel therapeutic target to inhibit SARS- CoV-2 viral uptake, as well as to decrease inflammatory and thrombotic MESHD effects through the modulation of the complement cascade.

    Soluble angiotensin-converting enzyme 2 HGNC is transiently elevated in COVID-19 MESHD and correlates with specific inflammatory and endothelial markers

    Authors: Annika Lundstrom; Louise Ziegler; Sebastian Havervall; Ann-Sofie Rudberg; Fien Von Meijenfeldt; Ton Lisman; Nigel Mackman; Per Sanden; Charlotte Thalin

    doi:10.1101/2021.03.03.21252841 Date: 2021-03-05 Source: medRxiv

    RationaleAngiotensin-converting enzyme 2 ( ACE2 HGNC) is the main entry receptor of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), but how SARS-CoV-2 interactions with ACE2 HGNC influences the renin-angiotensin system (RAS) in Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is unknown. ObjectiveTo measure circulating ACE2 HGNC and ACE HGNC levels in COVID-19 MESHD patients and investigate association with risk factors, outcome and inflammatory markers. Methods and resultsSoluble ACE2 HGNC (sACE2) and sACE concentrations were measured by ELISA in plasma samples from 114 hospital-treated COVID-19 MESHD patients and 10 healthy controls. Follow-up samples after four months were available for 58/114 patients. Von Willebrand MESHD Von Willebrand HGNC factor ( VWF HGNC), factor VIII ( fVIII HGNC), D-dimer, interleukin 6 ( IL-6 HGNC), tumor necrosis MESHD factor and plasminogen activator inhibitor 1 ( PAI-1 HGNC) had previously been determined. Levels of sACE2 were higher in COVID-19 MESHD patients than in healthy controls, median 5.0 (interquartile range 2.8-11.8) ng/ml versus 1.4 (1.1-1.6) ng/ml, p < 0.0001. sACE2 was higher in men than women, but were not affected by other risk factors for severe COVID-19 MESHD. sACE 2 decreased to 2.3 (1.6-3.9) ng/ml at follow-up, p < 0.0001, but remained higher than in healthy controls, p=0.012. Follow-up sACE2 levels were higher with increasing age, BMI, total number of comorbidities, for patients with diabetes MESHD and patients on RAS-inhibition. sACE was marginally lower during COVID-19 MESHD compared with at follow-up, 57 (45-70) ng/ml versus 72 (52-87) ng/ml, p=0.008. Levels of sACE2 and sACE did not differ depending on survival or disease severity (care level, respiratory support). sACE2 during COVID-19 MESHD correlated with VWF HGNC, fVIII HGNC and D-dimer, while sACE correlated with IL-6 HGNC, TNF HGNC and PAI-1 HGNC. ConclusionssACE2 was transiently elevated in COVID-19 MESHD, likely due to increased shedding from infected cells. sACE2 and sACE during COVID-19 MESHD differed distinctly in their correlations with markers of inflammation MESHD and endothelial dysfunction, suggesting release from different cell types and/or vascular beds.

    DNA damage contributes to age-associated differences in SARS-CoV-2 infection MESHD

    Authors: Rui Jin; Chang Niu; Fengyun Wu; Sixin Zhou; Tao Han; Zhe Zhang; Xiaona Zhang; Shanrong Xu; Jun Zhang; Xinyue Li; Yinggui Wang; Ting Gao; Mengnan Yu; Ruiguan Wang; Changjian Zhang; Jiangbo Li; Qi Liu; Haijing Zhao; Lingmei Qin; Yufang Li; Peng Yang; Shen Tian; Duoqi Zhou; Wei Chen; Qinong Ye; Cheng Cao; Long Cheng

    doi:10.21203/ Date: 2021-03-05 Source: ResearchSquare

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD), caused by coronavirus SARS-CoV-2 MESHD, is known to disproportionately affect older individuals. Age is the most important determinant of disease severity and mortality. How aging processes affect the disease progression remains largely unknown. Here we found that DNA damage, a common denominator and major cause of aging, promoted susceptibility to SARS-CoV-2 infection MESHD in cells and intestinal organoids. SARS-CoV-2 entry was facilitated by DNA damage caused by either telomere attrition or extrinsic genotoxic stress and hampered by inhibition of DNA damage response. Mechanistic analysis revealed that the DNA damage response increased expression of ACE2 HGNC, the receptor of SARS-CoV-2, by activation of transcription factor c-Jun HGNC in vitro and in vivo. Knockdown of c-Jun HGNC significantly reduced cell susceptibility to SARS-CoV-2. To explore the clinical clues of contribution of DNA damage in SARS-CoV-2 infection MESHD, we analyzed the expression of ACE2 HGNC, γH2Ax and p- c-Jun HGNC in old and young human and mouse tissues. Expression of ACE2 HGNC was elevated in older human and mouse tissues and positively correlated with γH2Ax and p-c-Jun. Finally, targeting DNA damage by increasing the DNA repair capacity, alleviated cell susceptibility to SARS-CoV-2. Our data provide insight into the age-associated differences in SARS-CoV-2 infection MESHD and a novel target for anti-viral intervention.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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