Corpus overview


Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (41)

ProteinN (3)

ProteinE (1)

ORF8 (1)


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SARS-CoV-2 Proteins
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    Ultrastructural insight into SARS-CoV-2 attachment, entry and budding in human airway epithelium

    Authors: Andreia L Pinto; Ranjit K Rai; Jonathan C Brown; Paul Griffin; James R Edgar; Anand Shah; Aran Singanayagam; Claire Hogg; Wendy S Barclay; Clare E Futter; Thomas Burgoyne

    doi:10.1101/2021.04.10.439279 Date: 2021-04-11 Source: bioRxiv

    Ultrastructural studies of SARS-CoV-2 infected MESHD cells are crucial to better understand the mechanisms of viral entry and budding within host cells. Many studies are limited by the lack of access to appropriate cellular models. As the airway epithelium is the primary site of infection it is essential to study SARS-CoV-2 infection MESHD of these cells. Here, we examined human airway epithelium, grown as highly differentiated air-liquid interface cultures and infected with three different isolates of SARS-CoV-2 including the B.1.1.7 variant (Variant of Concern 202012/01) by transmission electron microscopy and tomography. For all isolates, the virus infected ciliated but not goblet epithelial cells. Two key SARS-CoV-2 entry molecules, ACE2 HGNC and TMPRSS2 HGNC, were found to be localised to the plasma membrane including microvilli but excluded from cilia. Consistent with these observations, extracellular virions were frequently seen associated with microvilli and the apical plasma membrane but rarely with ciliary membranes. Profiles indicative of viral fusion at the apical plasma membrane demonstrate that the plasma membrane is one site of entry where direct fusion releasing the nucleoprotein PROTEIN-encapsidated genome occurs. Intact intracellular virions were found within ciliated cells in compartments with a single membrane bearing S glycoprotein PROTEIN. Profiles strongly suggesting viral budding from the membrane was observed in these compartments and this may explain how virions gain their S glycoprotein PROTEIN containing envelope.

    Genome-wide CRISPR activation screen identifies novel receptors for SARS-CoV-2 entry MESHD

    Authors: Shiyou Zhu; Ying Liu; Zhuo Zhou; Zhiying Zhang; Xia Xiao; Zhiheng Liu; Ang Chen; Xiaojing Dong; Feng Tian; Shihua Chen; Yiyuan Xu; Chunhui Wang; Qiheng Li; Xuran Niu; Qian Pan; Shuo Du; Junyu Xiao; Jianwei Wang; Wensheng Wei

    doi:10.1101/2021.04.08.438924 Date: 2021-04-09 Source: bioRxiv

    The ongoing pandemic of coronavirus disease 2019 MESHD ( COVID-19 MESHD) caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has been endangering worldwide public health and economy. SARS-CoV-2 infects MESHD a variety of tissues where the known receptor ACE2 HGNC is low or almost absent, suggesting the existence of alternative pathways for virus entry. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection MESHD. In addition to known host proteins, i.e PROTEIN. ACE2 HGNC, TMPRSS2 HGNC, and NRP1 HGNC, we identified multiple host components, among which LDLRAD3 HGNC, TMEM30A HGNC, and CLEC4G HGNC were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spike's N-terminal domain ( NTD HGNC). Their essential and physiological roles have all been confirmed in either neuron or liver cells. In particular, LDLRAD3 HGNC and CLEC4G HGNC mediate SARS-CoV-2 entry MESHD and infection in a fashion independent of ACE2 HGNC. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of the therapeutic countermeasures against COVID-19 MESHD.

    Coagulation factors directly cleave SARS-CoV-2 spike PROTEIN and enhance viral entry MESHD

    Authors: Edward R Kastenhuber; Javier A. Jaimes; Jared L. Johnson; Marisa Mercadante; Frauke Muecksch; Yiska Weisblum; Yaron Bram; Robert E. Schwartz; Gary R. Whittaker; Lewis C. Cantley

    doi:10.1101/2021.03.31.437960 Date: 2021-04-01 Source: bioRxiv

    Coagulopathy is recognized as a significant aspect of morbidity in COVID-19 MESHD patients. The clotting cascade is propagated by a series of proteases, including factor Xa HGNC and thrombin HGNC. Other host proteases, including TMPRSS2 HGNC, are recognized to be important for cleavage activation of SARS-CoV-2 spike PROTEIN to promote viral entry. Using biochemical and cell-based assays, we demonstrate that factor Xa HGNC and thrombin HGNC can also directly cleave SARS-CoV-2 spike PROTEIN, enhancing viral entry. A drug-repurposing screen identified a subset of protease inhibitors that promiscuously inhibited spike cleavage by both transmembrane serine proteases as well as coagulation factors. The mechanism of the protease inhibitors nafamostat and camostat extend beyond inhibition of TMPRSS2 HGNC to coagulation-induced spike cleavage. Anticoagulation is critical in the management of COVID-19 MESHD, and early intervention could provide collateral benefit by suppressing SARS-CoV-2 viral entry. We propose a model of positive feedback whereby infection-induced hypercoagulation MESHD exacerbates SARS-CoV-2 infectivity MESHD.

    TMPRSS2 HGNC inhibitor discovery facilitated through an in silico and biochemical screening platform

    Authors: Amanda L Peiffer; Julie M Garlick; Yujin Wu; Matthew B Soellner; Charles L Brooks III; Anna K Mapp

    doi:10.1101/2021.03.22.436465 Date: 2021-03-22 Source: bioRxiv

    The COVID-19 pandemic MESHD has highlighted the need for new antiviral targets, as many of the currently approved drugs have proven ineffective against mitigating SARS-CoV-2 infections MESHD. The host transmembrane serine protease HGNC TMPRSS2 HGNC is a highly promising antiviral target, as it plays a direct role in priming the spike protein PROTEIN before viral entry occurs. Further, unlike other targets such as ACE2 HGNC, TMPRSS2 HGNC has no known biological role. Here we utilize virtual screening to curate large libraries into a focused collection of potential inhibitors. Optimization of a recombinant expression and purification protocol for the TMPRSS2 HGNC peptidase domain facilitates subsequent biochemical screening and characterization of selected compounds from the curated collection in a kinetic assay. In doing so, we demonstrate that serine protease HGNC inhibitors camostat, nafamostat, and gabexate inhibit through a covalent mechanism. We further identify new non-covalent compounds as TMPRSS2 HGNC protease inhibitors, demonstrating the utility of a combined virtual and experimental screening campaign in rapid drug discovery efforts.

    The inhibitory effects of toothpaste and mouthwash ingredients on the interaction between the SARS-CoV-2 spike PROTEIN protein and ACE2 HGNC, and the protease activity of TMPRSS2 HGNC, in vitro

    Authors: Riho Tateyama-Makino; Mari Abe-Yutori; Taku Iwamoto; Kota Tsutsumi; Motonori Tsuji; Satoru Morishita; Kei Kurita; Yukio Yamamoto; Eiji Nishinaga; Keiichi Tsukinoki

    doi:10.1101/2021.03.19.435740 Date: 2021-03-19 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) enters host cells when the viral spike protein PROTEIN is cleaved by transmembrane protease serine 2 HGNC ( TMPRSS2 HGNC) after binding to the host angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC). Since ACE2 HGNC and TMPRSS2 HGNC are expressed in the mucosa of the tongue and gingiva, the oral cavity seems like it is an entry point for SARS-CoV-2. Daily oral care using mouthwash seems to play an important role in preventing SARS-CoV-2 infection MESHD. However, the relationship between daily oral care and the mechanisms of virus entry into host cells is unclear. In this study, we evaluated the inhibitory effects of ingredients that are generally contained in toothpaste and mouthwash on the interaction between the spike protein PROTEIN and ACE2 HGNC and on the serine protease HGNC activity of TMPRSS2 HGNC using an enzyme-linked immunosorbent assay and in vitro enzyme assay, respectively. Both assays detected inhibitory effects of sodium tetradecene sulfonate, sodium N-lauroyl-N-methyltaurate, sodium N-lauroylsarcosinate MESHD, sodium dodecyl sulfate, and copper gluconate. Molecular docking simulations suggested that these ingredients could bind to the inhibitor-binding site of ACE2 HGNC. In addition, tranexamic acid and 6-aminohexanoic acid, which act as serine protease HGNC inhibitors, exerted inhibitory effects on TMPRSS2 HGNC protease activity. Further experimental and clinical studies are needed to further elucidate these mechanisms. Our findings support the possibility that toothpaste and mouthwash contain ingredients that inhibit SARS-CoV-2 infection MESHD.

    Replication kinetic, cell tropism and associated immune responses in SARS-CoV-2 and H5N1 virus infected human iPSC derived neural models

    Authors: Lisa Bauer; Bas Lendemeijer; Lonneke Leijten; Carmen W. E. Embregts; Barry Rockx; Steven Aaron Kushner; Femke M.S. de Vrij; Debby van Riel

    doi:10.1101/2021.03.15.435472 Date: 2021-03-16 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection MESHD is associated with a wide variety of neurological complications MESHD. Even though SARS-CoV-2 is rarely detected in the central nervous system (CNS) or cerebrospinal fluid, evidence is accumulating that SARS-CoV-2 might enter the CNS via the olfactory nerve. However, what happens after SARS-CoV-2 enters the CNS is poorly understood. Therefore, we investigated the replication kinetics, cell tropism, and associated immune responses of SARS-CoV-2 infection MESHD in different types of neural cultures derived from human induced pluripotent stem cells (hiPSCs). SARS-CoV-2 was compared to the neurotropic and highly pathogenic H5N1 influenza A virus. SARS-CoV-2 infected MESHD a minority of individual mature neurons, without subsequent virus replication and spread, despite ACE2 HGNC, TMPRSS2 HGNC and NPR1 HGNC expression in all cultures. However, this sparse infection did result in the production of type-III-interferons and IL-8 HGNC. In contrast, H5N1 virus replicated and spread very efficiently in all cell types in all cultures. Taken together, our findings support the hypothesis that neurological complications might result from local immune responses triggered by virus invasion, rather than abundant SARS-CoV-2 replication in the CNS.

    Clomipramine suppresses ACE2 HGNC-mediated SARS-CoV-2 entry MESHD

    Authors: Yuri Kato; Shigeru Yamada; Kazuhiro Nishiyama; Ayano Satsuka; Suyong Re; Daiki Tomokiyo; Jae Man Lee; Tomohiro Tanaka; Akiyuki Nishimura; Kenzo Yonemitsu; Hiroshi Asakura; Yuko Ibuki; Yumiko Imai; Noriho Kamiya; Kenji Mizuguchi; Takahiro Kusakabe; Yasunari Kanda; Motohiro Nishida

    doi:10.1101/2021.03.13.435221 Date: 2021-03-14 Source: bioRxiv

    Myocardial damage caused by the newly emerged coronavirus ( SARS-CoV-2) infection MESHD is one of key determinants of COVID-19 MESHD severity and mortality. SARS-CoV-2 entry to host cells are initiated by binding with its receptor, angiotensin converting enzyme (ACE) 2 HGNC, and the ACE2 HGNC abundance is thought to reflect the susceptibility to infection. Here, we found that clomipramine, a tricyclic antidepressant, potently inhibits SARS-CoV-2 infection MESHD and metabolic disorder MESHD in human iPS-derived cardiomyocytes. Among 13 approved drugs that we have previously identified as potential inhibitor of doxorubicin-induced cardiotoxicity MESHD, clomipramine showed the best potency to inhibit SARS-CoV-2 spike PROTEIN glycoprotein pseudovirus-stimulated ACE2 HGNC internalization. Indeed, SARS-CoV-2 infection MESHD to human iPS-derived cardiomyocytes (iPS-CMs) and TMPRSS2 HGNC-expressing VeroE6 cells were dramatically suppressed even after treatment with clomipramine. Furthermore, the combined use of clomipramine and remdesivir was revealed to synergistically suppress SARS-CoV-2 infection MESHD. Our results will provide the potentiality of clomipramine for the breakthrough treatment of severe COVID-19 MESHD.

    Initial Study on TMPRSS2 HGNC p.Val160Met Genetic Variant in COVID-19 MESHD patients

    Authors: Laksmi Wulandari; Berliana Hamidah; Cennikon Pakpahan; Nevy Shinta Damayanti; Neneng Dewi Kurniati; Christophorus Oetama Adiatmaja; Monica Rizky Wigianita; Soedarsono Soedarsono; Dominicus Husada; Damayanti Tinduh; Cita Rosita Sigit Prakoeswa; Anang Endaryanto; Ni Nyoman Tri Puspaningsih; Maria Inge Lusida; Kazufumi Shimizu; Delvac Oceandy

    doi:10.21203/rs.3.rs-292930/v1 Date: 2021-03-03 Source: ResearchSquare

    Background Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is a global health problem that causes millions of deaths worldwide. The clinical manifestation of COVID-19 MESHD widely varies from asymptomatic infection to severe pneumonia MESHD and systemic inflammatory disease MESHD. It is thought that host genetic variability may affect the host's response to the virus infection MESHD and thus cause severity of the disease. The SARS-CoV-2 virus requires interaction with its receptor complex in the host cells before infection. The transmembrane protease serine 2 HGNC ( TMPRSS2 HGNC) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. Therefore, in this study we investigated the correlation between a genetic variant within the human TMPRSS2 HGNC gene and COVID-19 MESHD severity and viral load.ResultsWe genotyped 95 patients with COVID-19 MESHD hospitalized in Dr Soetomo General Hospital and Indrapura Field Hospital (Surabaya, Indonesia) for the TMPRSS2 p HGNC.Val160Met polymorphism. Polymorphism was detected using a TaqMan assay. We then analysed the association between the presence of the genetic variant and disease severity and viral load. We did not observe any correlation between the presence of TMPRSS2 HGNC genetic variant with the severity of the disease. However, we identified significant association between the p.Val160Met polymorphism and the SARS-CoV-2 viral load, as estimated by the Ct value of the diagnostic nucleic acid amplification test. Furthermore, we observed a trend of association between the presence of the C allele and the mortality rate in patients with severe COVID-19 MESHD. ConclusionOur data indicate a possible association between TMPRSS2 HGNC p.Val160Met polymorphism and SARS-CoV-2 infectivity MESHD and the outcome of Covid-19 MESHD

    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.

    Membrane-Mediated Sars-cov-2 Host Cell Entry: Potential Inhibitory Roles of Terpenoids in Silico

    Authors: Gideon Ampoma Gyebi; Oludare Ogunyemi; Ibrahim M. Ibrahim; Olalekan B. Ogunro; Adegbenro P. Adegunloye; Saheed Afolabi

    doi:10.21203/rs.3.rs-259624/v1 Date: 2021-02-20 Source: ResearchSquare

    Targeting viral cell entry proteins is an emerging therapeutic strategy for inhibiting the first stage of SARS-CoV-2 infection MESHD. In this study, 106 bioactive terpenoids from African medicinal plants were screened through molecular docking analysis against human angiotensin-converting enzyme 2 HGNC ( hACE2 HGNC), human transmembrane protease serine 2 HGNC ( TMPRSS2 HGNC) and the S proteins PROTEIN of SARS-CoV-2, SARS-CoV MESHD and MERS-CoV. In silico ADMET and drug-likeness prediction, molecular dynamics simulation ( MDS MESHD), binding free energy calculations and clustering analysis of MDS trajectories were performed on the top docked compounds to respective targets. The results revealed eight terpenoids with high binding tendencies to the catalytic residues of different targets. Pentacyclic terpenoids: 24-methylene cycloartenol and isoiguesterin interacted with the hACE2 HGNC binding hotspots for the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN protein. 11-hydroxy-2 - (3,4-dihydroxybenzoyloxy) abieta -5,7,9 (11),13-tetraene-12-one, 11-hydroxy-2 -(4-hydroxybenzoyloxy)-abieta- 5,7,9(11),13-tetraene-12-one and other abietane diterpenes interacted strongly with the S1-specificy pocket of TMPRSS2 HGNC. 3-benzoylhosloppone and cucurbitacin interacted with the RBD and S2 subunit of SARS-CoV-2 spike PROTEIN protein respectively. The predicted druggable and ADMET favourable terpenoids formed structurally stable complexes in the simulated dynamics environment. These terpenoids provides core structure that can be exploited for further lead optimization to design drugs against SARS-CoV-2 cell mediated entry, subject to further in vitro and in vivo studies. 

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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