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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (99)

NSP5 (7)

ProteinN (4)

ComplexRdRp (4)

ProteinE (2)


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SARS-CoV-2 Proteins
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    Prediction of repurposed drugs for treating lung injury in COVID-19 MESHD

    Authors: Bing He; Lana Garmire

    id:2003.14333v2 Date: 2020-03-30 Source: arXiv

    Coronavirus disease MESHD ( COVID-19 MESHD) is an infectious disease MESHD discovered in 2019 and currently in outbreak across the world. Lung injury MESHD with severe respiratory failure MESHD is the leading cause of death MESHD in COVID-19 MESHD, brought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there still lacks efficient treatment for COVID-19 MESHD induced lung injury MESHD and acute respiratory failure MESHD. Inhibition of Angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) caused by spike protein PROTEIN of SARS-CoV-2 is the most plausible mechanism of lung injury MESHD in COVID-19 MESHD. We propose two candidate drugs, COL-3 (a chemically modified tetracycline) and CGP-60474 (a cyclin-dependent kinase inhibitor), for treating lung injuries MESHD in COVID-19 MESHD, based on their abilities to reverse the gene expression patterns in HCC515 cells treated with ACE2 HGNC inhibitor and in human COVID-19 MESHD patient lung tissues. Further bioinformatics analysis shows that twelve significantly enriched pathways (P-value <0.05) overlap between HCC515 cells treated with ACE2 HGNC inhibitor and human COVID-19 MESHD patient lung tissues, including signaling pathways known to be associated with lung injury MESHD such as TNF signaling, MAPK signaling and Chemokine signaling pathways. All these twelve pathways are targeted in COL-3 treated HCC515 cells, in which genes such as RHOA HGNC, RAC2 HGNC, FAS, CDC42 HGNC have reduced expression. CGP-60474 shares eleven of twelve pathways with COL-3 with common target genes such as RHOA HGNC. It also uniquely targets genes related to lung injury MESHD, such as CALR HGNC and MMP14 HGNC. In summary, this study shows that ACE2 HGNC inhibition is likely part of the mechanisms leading to lung injury MESHD in COVID-19 MESHD, and that compounds such as COL-3 and CGP-60474 have the potential as repurposed drugs for its treatment.

    Genomics-guided molecular maps of coronavirus targets in human cells: a path toward the repurposing of existing drugs to mitigate the pandemic

    Authors: Gennadi Glinsky

    id:2003.13665v1 Date: 2020-03-30 Source: arXiv

    Human genes required for SARS-CoV-2 entry into human cells, ACE2 HGNC and FURIN HGNC, were employed as baits to build genomics-guided maps of up-stream regulatory elements, their expression and functions in human body, including pathophysiologically-relevant cell types. Genes acting as repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR HGNC; GATA5 HGNC; SFTPC HGNC; HIF1a HGNC) and activators ( HMGA2 HGNC; INSIG1 HGNC) were then employed to identify existing drugs that could be repurposed to mitigate the coronavirus infection MESHD. Present analyses identify Vitamin D and Quercetin as promising pandemic mitigation agents. Gene expression profiles of Vitamin D and Quercetin activities and their established safety records as over-the-counter medicinal substances suggest that they may represent viable candidates for further assessment and considerations of their potential as coronavirus pandemic mitigation agents. Notably, gene set enrichment analyses and expression profiling experiments identify multiple drugs, most notably testosterone, dexamethasone, and doxorubicin, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of Testosterone versus Estradiol impacts on SCARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during coronavirus pandemic.

    Renin-Angiotensin-Aldosterone System: Double-Edged Sword in COVID-19 MESHD Infection

    Authors: Jana Burchfield

    id:202003.0365/v1 Date: 2020-03-25 Source: Preprints.org

    The role of the Renin-Angiotensin-Aldosterone System (RAAS) in Corona Virus Disease MESHD 2019 ( COVID-19 MESHD) infection has become a controversial topic of discussion. RAAS inhibitors, such as Angiotensin Converting Enzyme ( ACE HGNC) inhibitors and Angiotensin II receptor blockers (ARBs), which are used to treat cardiovascular diseases MESHD, have been implicated in potentially increasing cell surface levels of ACE2 HGNC. ACE2 HGNC is the host receptor for COVID-19 MESHD that was discovered in Wuhan, China in December 2019. Since December, COVID-19 MESHD has transmitted rapidly across the world and has become a global pandemic. COVID-19 MESHD is similar to the Middle East respiratory syndrome coronavirus (MERS-CoV MESHD) with the first case reported in Saudi Arabia in September 2012. COVID-19 MESHD, also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is also similar to SARS-CoV MESHD, which first infected humans in the Guangdong province of southern China in 2002, and caused an epidemic between November 2002 and July 2003. Both SARS-CoV MESHD and COVID-19 MESHD use ACE2 HGNC to enter host cells. ACE2 HGNC is primarily expressed in the mouth, lung, heart, esophagus, kidney, bladder, and intestines, and is a component of RAAS, which serves to maintain vascular tone and blood volume. Inhibition or activation of other components of RAAS has been shown to directly increase or decrease the expression and/or activity of ACE2 HGNC. Furthermore, RAAS-targeting therapeutics, such as ACE HGNC inhibitors and ARBs, have also been shown to regulate the expression and/or activity of ACE2 HGNC, albeit in animal models. Although these changes in ACE2 HGNC have been demonstrated only in animal models, there is no evidence that administration of RAAS-targeting therapeutics to humans for the treatment of hypertension MESHD, diabetes MESHD, and other cardiovascular diseases MESHD (e.g., myocardial infarction MESHD and heart failure MESHD) causes changes in ACE2 HGNC expression. Nor is there clinical evidence that RAAS-targeting therapeutics augment COVID-19 MESHD infection, morbidity, or mortality. However, clinical evidence does suggest that ACE2 HGNC expression may protect against respiratory distress MESHD caused by a variety of noxious agents. This review attempts to provide a balanced overview of the potential role of RAAS in regulating ACE2 HGNC, and the role of ACE2 HGNC during COVID-19 MESHD infection. Evidence is provided to show that the expression of ACE2 HGNC may mediate both positive and negative outcomes, depending on the timing of ACE2 HGNC expression.

    SARS-CoV-2, an evolutionary perspective of interaction with human ACE2 HGNC reveals undiscovered amino acids necessary for complex stability

    Authors: Vinicio Armijos-Jaramillo; Justin Yeager; Claire Muslin; Yunierkis Perez-Castillo

    doi:10.1101/2020.03.21.001933 Date: 2020-03-23 Source: bioRxiv

    The emergence of SARS-CoV-2 has resulted in more than 200,000 infections and nearly 9,000 deaths globally so far. This novel virus is thought to have originated from an animal reservoir, and acquired the ability to infect human cells using the SARS-CoV cell receptor hACE2 HGNC. In the wake of a global pandemic it is essential to improve our understanding of the evolutionary dynamics surrounding the origin and spread of a novel infectious disease MESHD. One way theory predicts selection pressures should shape viral evolution is to enhance binding with host cells. We first assessed evolutionary dynamics in select betacoronavirus spike protein PROTEIN genes to predict where these genomic regions are under directional or purifying selection between divergent viral lineages at various scales of relatedness. With this analysis, we determine a region inside the receptor-binding domain with putative sites under positive selection interspersed among highly conserved sites, which are implicated in structural stability of the viral spike protein PROTEIN and its union with human receptor hACE2 HGNC. Next, to gain further insights into factors associated with coronaviruses recognition of the human host receptor, we performed modeling studies of five different coronaviruses and their potential binding to hACE2 HGNC. Modeling results indicate that interfering with the salt bridges at hot spot 353 could be an effective strategy for inhibiting binding, and hence for the prevention of coronavirus infections MESHD. We also propose that a glycine residue at the receptor binding domain of the spike glycoprotein PROTEIN can have a critical role in permitting bat variants of the coronaviruses to infect human cells.

    The sequence of human ACE2 HGNC is suboptimal for binding the S spike protein PROTEIN of SARS coronavirus 2

    Authors: Erik Procko

    doi:10.1101/2020.03.16.994236 Date: 2020-03-17 Source: bioRxiv

    The rapid and escalating spread of SARS coronavirus MESHD 2 (SARS-CoV-2) poses an immediate public health emergency. The viral spike protein S PROTEIN binds ACE2 HGNC on host cells to initiate molecular events that release the viral genome intracellularly. Soluble ACE2 HGNC inhibits entry of both SARS and SARS-2 coronaviruses by acting as a decoy for S binding sites, and is a candidate for therapeutic, prophylactic and diagnostic development. Using deep mutagenesis, variants of ACE2 HGNC are identified with increased binding to the receptor binding domain of S. Mutations are found across the interface, in the N90-glycosylation motif, and at buried sites where they are predicted to enhance local folding and presentation of the interaction epitope. When single substitutions are combined, large increases in binding can be achieved. The mutational landscape offers a blueprint for engineering high affinity proteins and peptides that block receptor binding sites on S to meet this unprecedented challenge.

    SARS-CoV-2 Entry Genes Are Most Highly Expressed in Nasal Goblet and Ciliated Cells within Human Airways

    Authors: Waradon Sungnak; Ni Huang; Christophe Bécavin; Marijn Berg; HCA Lung Biological Network

    id:2003.06122v1 Date: 2020-03-13 Source: arXiv

    The SARS-CoV-2 coronavirus, the etiologic agent responsible for COVID-19 MESHD coronavirus disease MESHD, is a global threat. To better understand viral tropism, we assessed the RNA expression of the coronavirus receptor, ACE2 HGNC, as well as the viral S protein PROTEIN priming protease TMPRSS2 HGNC thought to govern viral entry in single-cell RNA-sequencing (scRNA-seq) datasets from healthy individuals generated by the Human Cell Atlas consortium. We found that ACE2 HGNC, as well as the protease TMPRSS2 HGNC, are differentially expressed in respiratory and gut epithelial cells. In-depth analysis of epithelial cells in the respiratory tree reveals that nasal epithelial cells, specifically goblet/secretory cells and ciliated cells, display the highest ACE2 HGNC expression of all the epithelial cells analyzed. The skewed expression of viral receptors/entry-associated proteins towards the upper airway may be correlated with enhanced transmissivity. Finally, we showed that many of the top genes associated with ACE2 HGNC airway epithelial expression are innate immune-associated, antiviral genes, highly enriched in the nasal epithelial cells. This association with immune pathways might have clinical implications for the course of infection and viral pathology, and highlights the specific significance of nasal epithelia in viral infection MESHD. Our findings underscore the importance of the availability of the Human Cell Atlas as a reference dataset. In this instance, analysis of the compendium of data points to a particularly relevant role for nasal goblet and ciliated cells as early viral targets and potential reservoirs of SARS-CoV-2 infection MESHD. This, in turn, serves as a biological framework for dissecting viral transmission and developing clinical strategies for prevention and therapy.

    The Small Intestine, an Underestimated Site of SARS-CoV-2 Infection MESHD: From Red Queen Effect to Probiotics

    Authors: Zhijie Feng; Yan Wang; Wei Qi

    id:10.20944/preprints202003.0161.v1 Date: 2020-03-10 Source: Preprints.org

    Understanding how the coronaviruses invade our body is an essential point, and the expression profile of coronaviruses receptor may help us to find where the coronavirus infects MESHD our body. We found that the coronavirus receptors, including angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) for SARS-CoV MESHD and SARS-Cov-2, are digestion-related enzymes in human enterocytes. Coronaviruses are continually altering the binding receptor and binding modes during their evolution, but the potential target cell in the small intestine is constant when in the lung is inconstant. Enterocytes may act as a conserved cell reservoir for coronaviruses, which may be partially explained by the Red Queen hypothesis. We also found that coronaviruses receptors could be elevated in the presence of both invasive bacteria MESHD and their counterpart, probiotics. We demonstrated here that enterocytes act as a conserved cell reservoir for coronaviruses during their evolutions, which should not be ignored in the investigation of coronavirus diagnosis and treatment strategies.

    Sequence variation of SARS-CoV-2 spike PROTEIN protein may facilitate stronger interaction with ACE2 HGNC promoting high infectivity

    Authors: Masaud Shah; Bilal Ahmad; Sangdun Choi; Hyun Goo Woo

    doi:10.21203/rs.3.rs-16932/v1 Date: 2020-03-09 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease MESHD ( COVID-19 MESHD), is a novel beta coronavirus emerged in China in 2019. Coronavirus uses spike glycoprotein PROTEIN to interact with host angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) and ensure cell recognition. High infectivity of SARS-CoV-2 raises questions on spike- ACE2 HGNC binding affinity and its neutralization by anti-SARS-CoV monoclonal antibodies (mAbs). Here, we observed Val-to-Lys417 mutation in the receptor-binding domains (RBD) of SARS-CoV-2, which established a Lys-Asp electrostatic interaction enhancing its ACE2 HGNC-binding. Pro-to-Ala475 substitution and Gly482 insertion in the AGSTPCNGV-loop of RBD hindered neutralization of SARS-CoV-2 by anti- SARS-CoV mAbs MESHD. In addition, we identified unique and structurally conserved conformational-epitopes on RBDs, which can be potential therapeutic targets. Collectively, we provide new insights into the mechanisms underlying the high infectivity of SARS-CoV-2 and development of new effective neutralizing agents.

    Increasing Host Cellular Receptor--Angiotensin-Converting Enzyme 2 ( ACE2 HGNC) Expression by Coronavirus may Facilitate 2019-nCoV Infection MESHD

    Authors: Pei-Hui Wang

    doi:10.1101/2020.02.24.963348 Date: 2020-02-27 Source: bioRxiv

    The ongoing outbreak of a new coronavirus (2019-nCoV) causes an epidemic of acute respiratory syndrome MESHD in humans. 2019-nCoV rapidly spread to national regions and multiple other countries, thus, pose a serious threat to public health. Recent studies show that spike (S) proteins PROTEIN of 2019-nCoV and SARS-CoV MESHD may use the same host cell receptor called angiotensin-converting enzyme 2 ( ACE2 HGNC) for entering into host cells. The affinity between ACE2 HGNC and 2019-nCoV S is much higher than ACE2 HGNC binding to SARS-CoV S protein MESHD S protein PROTEIN, explaining that why 2019-nCoV seems to be more readily transmitted from the human to human. Here, we reported that ACE2 HGNC can be significantly upregulated after infection of various viruses including SARS-CoV MESHD and MERS-CoV. Basing on findings here, we propose that coronavirus infection MESHD can positively induce its cellular entry receptor to accelerate their replication and spread, thus drugs targeting ACE2 HGNC expression may be prepared for the future emerging infectious diseases MESHD caused by this cluster of viruses.

    Structure of dimeric full-length human ACE2 HGNC in complex with B0AT HGNC1

    Authors: Qiang Zhou; Renhong Yan; Yuanyuan Zhang; Yaning Li; Lu Xia

    doi:10.1101/2020.02.17.951848 Date: 2020-02-18 Source: bioRxiv

    Angiotensin-converting enzyme 2 ( ACE2 HGNC) is the surface receptor for SARS coronavirus ( SARS-CoV MESHD), directly interacting with the spike glycoprotein PROTEIN ( S protein PROTEIN). ACE2 HGNC is also suggested to be the receptor for the new coronavirus (2019-nCoV), which is causing a serious epidemic in China manifested with severe respiratory syndrome MESHD. B0AT1 HGNC ( SLC6A19 HGNC) is a neutral amino acid transporter whose surface expression in intestinal cells requires ACE2 HGNC. Here we present the 2.9 [A] resolution cryo-EM structure of full-length human ACE2 HGNC in complex with B0AT1 HGNC. The complex, assembled as a dimer of ACE2 HGNC- B0AT1 HGNC heterodimers, exhibits open and closed conformations due to the shifts of the peptidase domains (PDs) of ACE2 HGNC. A newly resolved Collectrin-like domain (CLD) on ACE2 HGNC mediates homo-dimerization. Structural modelling suggests that the ACE2 HGNC- B0AT1 HGNC complex can bind two S proteins PROTEIN simultaneously, providing important clues to the molecular basis for coronavirus recognition and infection MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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