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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (100)

NSP5 (7)

ProteinN (4)

ComplexRdRp (4)

ProteinE (2)


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SARS-CoV-2 Proteins
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    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

    Authors:

    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/rs.3.rs-301544/v1 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.

    SARS-CoV-2 Viremia MESHD is Associated with Distinct Proteomic Pathways and Predicts COVID-19 MESHD Outcomes

    Authors: Yijia Li; Alexis M Schneider; Arnav Mehta; Moshe Sade-Feldman; Kyle R Kays; Matteo Gentili; Nicole C Charland; Anna LK Gonye; Irena Gushterova; Hargun K Khanna; Thomas J LaSalle; Kendall M Lavin-Parsons; Brendan M Lilley; Carl L Lodenstein; Kasidet Manakongtreecheep; Justin D Margolin; Brenna N McKaig; Blair A Parry; Maricarmen Rojas-Lopez; Brian C Russo; Nihaarika Sharma; Jessica Tantivit; Molly F Thomas; James Regan; James P Flynn; Alexandra-Chloe Villani; Nir Hacohen; Marcia B Goldberg; Michael R Filbin; Jonathan Z Li

    doi:10.1101/2021.02.24.21252357 Date: 2021-02-26 Source: medRxiv

    Background: Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2) plasma viremia MESHD has been associated with severe disease and death in coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) in small-scale cohort studies. The mechanisms behind this association remain elusive. Methods: We evaluated the relationship between SARS-CoV-2 viremia MESHD, disease outcome, inflammatory and proteomic profiles in a cohort of COVID-19 MESHD emergency department participants. SARS-CoV-2 viral load was measured using qRT-PCR based platform. Proteomic data were generated with Proximity Extension Assay (PEA) using the Olink platform. Results: Three hundred participants with nucleic acid test-confirmed COVID-19 MESHD were included in this study. Levels of plasma SARS-CoV-2 viremia MESHD at the time of presentation predicted adverse disease outcomes, with an adjusted odds ratio (aOR) of 10.6 (95% confidence interval [CI] 4.4, 25.5, P<0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and aOR of 3.9 (95%CI 1.5, 10.1, P=0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia MESHD, including upregulation of SARS-CoV-2 entry factors ( ACE2 HGNC, CTSL HGNC, FURIN HGNC), heightened markers of tissue damage to the lungs, gastrointestinal tract, endothelium/vasculature and alterations in coagulation pathways. Conclusions: These results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia MESHD that underlies its ability to predict COVID-19 MESHD disease outcomes.

    Comprehensive evaluation of ACE2 HGNC expression in female ovary by single-cell RNA-seq analysis

    Authors: Siming Kong; Zhiqiang Yan; Peng Yuan; Xixi Liu; Yidong Chen; Ming Yang; Wei Chen; Shi Song; Jie Yan; Liying Yan; Jie Qiao

    doi:10.1101/2021.02.23.432460 Date: 2021-02-23 Source: bioRxiv

    Pneumonia induced by severe acute respiratory coronavirus MESHD 2 (SARS-CoV-2) via ACE2 HGNC receptor may affect many organ systems like lung, heart and kidney. An autopsy report revealed positive SARS-Cov-2 detection results in ovary MESHD, however, the developmental-stage-specific and cell-type-specific risk in fetal primordial germ cells (PGCs) and adult women ovary remained unclear. In this study, we used single-cell RNA-sequencing (scRNA-seq) datasets spanning several developmental stages of ovary MESHD including PGCs and cumulus-oocyte complex (COC) to investigate the potential risk of SARS-CoV-2 infection MESHD. We found that PGCs and COC exhibited high ACE2 HGNC expression. More importantly, the ratio of ACE2 HGNC-positive cells was sharply up-regulated in primary stage and ACE2 HGNC was expressed in all oocytes and cumulus cells in preovulatory stage, suggesting the possible risk of SARS-CoV-2 infection MESHD in follicular development. CatB HGNC/L, not TMPRSS2 HGNC, was identified to prime for SARS-CoV-2 entry MESHD in follicle. Our findings provided insights into the potential risk of SARS-CoV-2 infection MESHD during folliculogenesis in adulthood and the possible risk in fetal PGCs.

    A Potential Impact of SARS-CoV-2 on Pituitary Glands and Pituitary Neuroendocrine Tumors MESHD

    Authors: Wei Ting Gu; Fen Zhou; Wan Qun Xie; Shuo Wang; Hong Yao; Yan Ting Liu; Ling Gao; Zhe Bao Wu

    doi:10.21203/rs.3.rs-271362/v1 Date: 2021-02-23 Source: ResearchSquare

    Introduction: Angiotensin-converting enzyme 2 (ACE2) is the receptor of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). The effects of SARS-CoV-2 on normal pituitary glands function or pituitary neuroendocrine tumors MESHD ( PitNETs MESHD) have not yet been elucidated. Thus, the present study aimed to investigate the potential risks of SARS-CoV-2 infection MESHD on the impairment of pituitary glands MESHD and the development of PitNETs MESHD.Methods: PitNETs MESHD tissues were obtained from 114 patients, and normal pituitary gland tissues were obtained from the autopsy. The mRNA levels of ACE2 HGNC and angiotensin II receptor type 1 HGNC ( AGTR1 HGNC) were examined by quantitative real-time PCR. Immunohistochemical staining was performed for ACE2 HGNC in 69 PitNETs MESHD and 3 normal pituitary glands. The primary tumor MESHD cells and pituitary cell lines (MMQ, GH3 and AtT-20/D16v-F2) were treated with diminazene aceturate (DIZE), an ACE2 HGNC agonist, with various dose regimens. The pituitary hormones between 43 patients with SARS-CoV-2 infection MESHD were compared with 45 healthy controls.Results: Pituitary glands and the majority of PitNET tissues showed low/negative ACE2 HGNC expression at both the mRNA and protein levels, while AGTR1 HGNC showed high expression in normal pituitary and corticotroph adenomas MESHD. ACE2 agonist increased the secretion of ACTH in AtT-20/D16v-F2 cells through downregulating AGTR1. The level of serum adrenocorticotropic hormone ( ACTH HGNC) was significantly increased in COVID-19 MESHD patients as compared to normal controls (p<0.001), but was dramatically decreased in critical cases as compared to non-critical patients (p=0.003).Conclusion: This study revealed a potential impact of SARS-CoV-2 infection MESHD on corticotroph cells and adenomas MESHD.

    Sensing of cytoplasmic chromatin by cGAS activates innate immune response in SARS-CoV-2 infection MESHD

    Authors: Zhuo Zhou; Xinyi Zhang; Xiaobo Lei; Xia Xiao; Tao Jiao; Ruiyi Ma; Xiaojing Dong; Qi Jiang; Wenjing Wang; Yujin Shi; Tian Zheng; Yuting Tan; Zichun Xiang; Lili Ren; Tao Deng; Zhengfan Jiang; Zhixun Dou; Wensheng Wei; Jianwei Wang

    doi:10.21203/rs.3.rs-235742/v1 Date: 2021-02-12 Source: ResearchSquare

    The global coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic is caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection MESHD remain to be determined. Here, we report that SARS-CoV-2 infection MESHD activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection MESHD induces the cellular level of 2'3'-cGAMP associated with STING activation. cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection MESHD. We further demonstrate that the expression of spike protein PROTEIN from SARS-CoV-2 and ACE2 HGNC from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion. Furthermore, cytoplasmic chromatin-cGAS-STING pathway, but not MAVS HGNC mediated viral RNA sensing pathway, contributes to interferon and pro-inflammatory gene expression upon cell fusion. Finally, we show that cGAS is required for host antiviral responses against SARS-CoV-2, and a STING-activating compound potently inhibits viral replication. Together, our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection MESHD, mediated by cytoplasmic chromatin from the infected cells. Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19 MESHD. In addition, these findings extend our knowledge in host defense against viral infection MESHD by showing that host cells’ self-nucleic acids can be employed as a “danger signal” to alarm the immune system.

    Differential roles of RIG-I HGNC-like receptors in SARS-CoV-2 infection MESHD

    Authors: Duomeng Yang; Tingting Geng; Andrew G Harrison; PENGHUA WANG

    doi:10.1101/2021.02.10.430677 Date: 2021-02-11 Source: bioRxiv

    The retinoic acid-inducible gene I ( RIG-I HGNC) and melanoma MESHD melanoma HGNC differentiation-associated protein 5 ( MDA5 HGNC) are the major viral RNA sensors that are essential for activation of antiviral immune responses. However, their roles in severe acute respiratory syndrome MESHD (SARS)-causing coronavirus (CoV) infection MESHD are largely unknown. Herein we investigate their functions in human epithelial cells, the primary and initial target of SARS-CoV-2, and the first line of host defense. A deficiency in MDA5 HGNC ( MDA5 HGNC-/-), RIG-I HGNC or mitochondrial antiviral signaling protein HGNC ( MAVS HGNC) greatly enhanced viral replication. Expression of the type I/III interferons (IFN) HGNC was upregulated following infection in wild-type cells, while this upregulation was severely abolished in MDA5 HGNC-/- and MAVS HGNC-/-, but not in RIG-I HGNC-/- cells. Of note, ACE2 HGNC expression was ~2.5 fold higher in RIG-I HGNC-/- than WT cells. These data demonstrate a dominant role of MDA5 HGNC in activating the type I/III IFN response to SARS-CoV-2, and an IFN HGNC-independent anti-SARS-CoV-2 role of RIG-I HGNC.

    Protein corona critically affects the bio-behaviors of SARS-CoV-2

    Authors: Yue-wen Yin; Yan-jing Sheng; Min Wang; Song-di Ni; Hong-ming Ding; Yu-qiang Ma

    id:2102.05440v1 Date: 2021-02-10 Source: arXiv

    The outbreak of the coronavirus disease 2019 MESHD ( COVID-19 MESHD) caused by severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) has become a worldwide public health crisis. When the SARS-CoV-2 enters the biological fluids in the human body, different types of biomolecules (in particular proteins) may adsorb on its surface and alter its infection ability. Although great efforts have recently been devoted to the interaction of the specific antibodies with the SARS-CoV-2, it still remains largely unknown how the other serum proteins affect the infection of the SARS-CoV-2. In this work, we systematically investigate the interaction of serum proteins with the SARS-CoV-2 RBD by the molecular docking and the all-atom molecular dynamics simulations. It is found that the non-specific immunoglobulin (Ig) indeed cannot effectively bind to the SARS-CoV-2 RBD while the human serum albumin (HSA) may have some potential of blocking its infection (to ACE2 HGNC). More importantly, we find that the RBD can cause the significant structural change of the Apolipoprotein E HGNC ( ApoE HGNC), by which SARS-CoV-2 may hijack the metabolic pathway of the ApoE HGNC to facilitate its cell entry. The present study enhances the understanding of the role of protein corona in the bio-behaviors of SARS-CoV-2, which may aid the more precise and personalized treatment for COVID-19 MESHD infection in the clinic.

    Transformations, Comparisons, and Analysis of Down to Up Protomer States of Variants of the SARS-CoV-2 Prefusion Spike Protein PROTEIN Including the UK Variant B.1.1.7

    Authors: michael h peters; Oscar Basidas; Daniel Kokron; Christopher E. Henze

    doi:10.1101/2021.02.09.430519 Date: 2021-02-09 Source: bioRxiv

    Monitoring and strategic response to variants in SARS-CoV-2 represents a considerable challenge in the current pandemic, as well as potentially future viral outbreaks of similar magnitude. In particular mutations and deletions involving the virion's prefusion Spike protein PROTEIN has significant potential impact on vaccines and therapeutics that utilize this key structural viral protein in their mitigation strategies. In this study, we have demonstrated how dominant energetic landscape mappings ("glue points") coupled with sequence alignment information can potentially identify or flag key residue mutations and deletions associated with variants. Surprisingly, we also found excellent homology of stabilizing residue glue points across the lineage of $\beta$ coronavirus Spike proteins MESHD Spike proteins PROTEIN, and we have termed this as "sequence homologous glue points". In general, these flagged residue mutations and/or deletions are then computationally studied in detail using all-atom biocomputational molecular dynamics over approximately one microsecond in order to ascertain structural and energetic changes in the Spike protein PROTEIN associated variants. Specifically, we examined both a theoretically-based triple mutant and the so-called UK or B.1.1.7 variant. For the theoretical triple mutant, we demonstrated through Alanine mutations, which help "unglue" key residue-residue interactions, that these three key stabilizing residues could cause the transition of Down to Up protomer states, where the Up protomer state allows binding of the prefusion Spike protein PROTEIN to hACE2 HGNC host cell receptors, whereas the Down state is believed inaccessible. For the B.1.1.7 variant, we demonstrated the critical importance of D614G and N5017 on the structure and binding of the Spike protein PROTEIN associated variant. In particular, we had previously identified D614 as a key glue point in the inter-protomer stabilization of the Spike protein PROTEIN. Other mutations and deletions associated with this variant did not appear to play a pivotal role in structure or binding changes. The mutant D614G is a structure breaking Glycine mutation demonstrating a relatively large hinge angle and highly stable Up conformation in agreement with previous studies. In addition, we demonstrate that the mutation N501Y may significantly increase the Spike protein PROTEIN binding to hACE2 HGNC cell receptors through its interaction with Y41 of hACE2 HGNC forming a potentially strong hydrophobic residue binding pair. We note that these two key mutations, D614G and N501Y, are also found in the so-called South African (SA; B.1.351) variant of SARS-CoV-2. Future studies along these lines are therefore aimed at mapping glue points to residue mutations and deletions of associated prefusion Spike protein PROTEIN variants in order to help direct and optimize efforts aimed at the mitigation of this deadly virion.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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