Corpus overview


Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (71)

ProteinN (5)

ProteinE (2)

NSP5 (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.

    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.

    Placental expression of ACE2 HGNC and TMPRSS2 HGNC in maternal SARS-CoV-2 infection MESHD: are placental defenses mediated by fetal sex?

    Authors: Lydia L Shook; Evan A Bordt; Marie-Charlotte Meinsohn; David Pepin; Rose M De Guzman; Sara Brigada; Laura J Yockey; Kaitlyn E James; Mackenzie W Sullivan; Lisa M Bebell; Drucilla J Roberts; Anjali J Kaimal; Danny Schust; Andrea G Edlow

    doi:10.1101/2021.04.01.438089 Date: 2021-04-01 Source: bioRxiv

    Background: Sex differences in vulnerability to and severity of SARS-CoV-2 infection MESHD have been described in non-pregnant populations. ACE2 HGNC and TMPRSS2 HGNC, host molecules required for viral entry, are regulated by sex steroids and expressed in the placenta. We sought to investigate whether placental ACE2 HGNC and TMPRSS2 HGNC expression vary by fetal sex and in the presence of maternal SARS-CoV-2 infection MESHD. Methods: Placental ACE2 HGNC and TMPRSS2 HGNC were quantified in 68 pregnant individuals (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. Maternal SARS-CoV-2 status was determined by nasopharyngeal RT-PCR. Placental SARS-CoV-2 viral load was quantified. RTqPCR was performed to quantify expression of ACE2 HGNC and TMPRSS2 HGNC relative to the reference gene YWHAZ HGNC. Western blots were performed on placental homogenates to quantify protein levels. The impact of fetal sex and SARS-CoV-2 exposure on ACE2 HGNC and TMPRSS2 HGNC expression was analyzed by 2-way ANOVA. Results: SARS-CoV-2 virus was undetectable in all placentas. Maternal SARS-CoV-2 infection MESHD impacted TMPRSS2 HGNC placental gene and protein expression in a sexually dimorphic fashion (2-way ANOVA interaction p-value: 0.002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on placental ACE2 HGNC gene or protein expression. Placental TMPRSS2 HGNC expression was significantly correlated with ACE2 HGNC expression in males (Spearman's rho=0.54, p=0.02) but not females (rho=0.23, p=0.34) exposed to maternal SARS-CoV-2. Conclusions: Sex differences in placental TMPRSS2 HGNC but not ACE2 HGNC were observed in the setting of maternal SARS-CoV-2 infection MESHD. These findings may have implications for offspring vulnerability to placental infection and vertical transmission.These findings may have implications for offspring vulnerability to placental infection and vertical transmission.

    Enrichment of SARS-CoV-2 entry factors and interacting intracellular genes in peripheral immune cells

    Authors: Abhinandan Devaprasad; Aridaman Pandit

    doi:10.1101/2021.03.29.437515 Date: 2021-03-29 Source: bioRxiv

    SARS-CoV-2 uses ACE2 HGNC and TMPRSS2 HGNC to gain entry into the cell. However, recent studies have shown that SARS-CoV-2 may use additional host factors that are required for the viral lifecycle. Here we used publicly available datasets, CoV associated genes and machine learning algorithms to explore the SARS-CoV-2 interaction landscape in different tissues. We find that in general a small fraction of cells expresses ACE2 HGNC in the different tissues including nasal, bronchi and lungs. We show that a small fraction of immune cells (including T-cells, macrophages, dendritic cells) found in tissues also express ACE2 HGNC. We show that healthy circulating immune cells do not express ACE2 HGNC and TMPRSS2 HGNC. However, a small fraction of circulating immune cells (including dendritic cells, monocytes, T-cells) in the PBMC of COVID-19 MESHD patients express ACE2 HGNC and TMPRSS2 HGNC. Additionally, we found that a large spectrum of cells (in circulation and periphery) in both healthy and COVID-19 MESHD positive patients were significantly enriched for SARS-CoV-2 factors. Thus, we propose that further research is needed to explore if SARS-CoV-2 can directly infect peripheral immune cells to better understand the virus' mechanism of action.

    Age-dependent appearance of SARS-CoV-2 entry cells in mouse chemosensory systems reflects COVID-19 MESHD anosmia MESHD and ageusia symptoms MESHD.

    Authors: Julien Brechbuhl; Dean Wood; Sofiane Bouteiller; Ana Catarina Lopes; Chantal Verdumo; Marie-Christine Broillet

    doi:10.1101/2021.03.29.437530 Date: 2021-03-29 Source: bioRxiv

    COVID-19 pandemic MESHD has given rise to a collective scientific effort to study its viral causing agent SARS-CoV-2. Research is focusing in particular on its infection mechanisms and on the associated-disease symptoms. Interestingly, this environmental pathogen directly affects the human chemosensory systems leading to anosmia and ageusia MESHD. Evidence for the presence of the cellular entry sites of the virus, the ACE2 HGNC and the TMPRSS2 HGNC proteins, has been reported in non-chemosensory cells in the nose and mouth of the rodents, missing a direct correlation between the symptoms reported in patients and the observed direct viral infection in human sensory cells. Here, mapping the gene and protein expression of ACE2 and TMPRSS2 in the mouse olfactory and gustatory cells, we precisely identified the virus target cells to be of basal and sensory origin and we revealed their age-dependent appearance. Our results not only clarify human viral-induced sensory symptoms but also propose new investigative perspectives based on ACE2 HGNC-humanized mouse models.

    Antidepressant and antipsychotic drugs reduce viral infection MESHD by SARS-CoV-2 and fluoxetine show antiviral activity against the novel variants in vitro

    Authors: Merve Senem Fred; Suvi Kuivanen; Hasan Ugurlu; Plinio Cabrera Casarotto; Lev Levanov; Kalle Saksela; Olli Vapalahti; Eero Castren

    doi:10.1101/2021.03.22.436379 Date: 2021-03-23 Source: bioRxiv

    Background and Purpose: Repurposing of currently available drugs is a valuable strategy to tackle the consequences of COVID-19 MESHD. Recently, several studies have investigated the effect of psychoactive drugs on SARS-CoV-2 in cell culture models as well as in clinical practice. Our aim was to expand these studies and test some of these compounds against newly emerged variants. Experimental Approach: Several antidepressant drugs and antipsychotic drugs with different primary mechanisms of action were tested in ACE2 HGNC/ TMPRSS2 HGNC-expressing human embryonic kidney cells against the infection by SARS-CoV-2 spike PROTEIN protein-dependent pseudoviruses. Some of these compounds were also tested in human lung epithelial cell line, Calu-1, against the first wave (B.1) lineage of SARS-CoV-2 and the variants of concern, B.1.1.7 and B.1.351. Key Results: Several clinically used antidepressants, including fluoxetine, citalopram, reboxetine, imipramine, as well as antipsychotic compounds chlorpromazine, flupenthixol, and pimozide inhibited the infection by pseudotyped viruses with minimal effects on cell viability. The antiviral action of several of these drugs was verified in Calu-1 cells against the (B.1) lineage of SARS-CoV-2. By contrast, the anticonvulsant carbamazepine, and novel antidepressants ketamine and its derivatives as well as MAO and phosphodiesterase inhibitors phenelzine and rolipram, respectively, showed no activity in the pseudovirus model. Furthermore, fluoxetine remained effective against pseudo viruses with N501Y, K417N, and E484K spike mutations, and the VoC-1 (B.1.1.7) and VoC-2 (B.1.351) variants of SARS-CoV-2. Conclusion and Implications: Our study confirms previous data and extends information on the repurposing of these drugs to counteract SARS-CoV-2 infection MESHD including different variants of concern.

    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.

    Common dandelion (Taraxacum officinale) efficiently blocks the interaction between ACE2 cell surface receptor and SARS-CoV-2 spike PROTEIN protein D614, mutants D614G, N501Y, K417N and E484K in vitro

    Authors: Hoai Thi Thu Tran; Nguyen Phan Khoi Le; Michael Gigl; Corinna Dawid; Evelyn Lamy

    doi:10.1101/2021.03.19.435959 Date: 2021-03-19 Source: bioRxiv

    On 11th March 2020, coronavirus disease 2019 MESHD ( COVID-19 MESHD), caused by the SARS-CoV-2 virus, was declared as a global pandemic by the World Health Organization (WHO). To date, there are rapidly spreading new "variants of concern" of SARS-CoV-2, the United Kingdom (B.1.1.7), the South African (B.1.351) or Brasilian (P.1) variant. All of them contain multiple mutations in the ACE2 HGNC receptor recognition site of the spike protein PROTEIN, compared to the original Wuhan sequence, which is of great concern, because of their potential for immune escape. Here we report on the efficacy of dandelion (Taraxacum officinale) to block protein-protein interaction of spike S1 to the human ACE2 cell surface receptor. This could be shown for the original spike D614, but also for its mutant forms (D614G, N501Y, and mix of K417N, E484K, N501Y) in human HEK293- hACE2 HGNC kidney and A549- hACE2 HGNC- TMPRSS2 HGNC lung cells. High molecular weight compounds in the water-based extract account for this effect. Infection of lung cells using SARS-CoV-2 spike PROTEIN pseudotyped lentivirus particles was efficiently prevented by the extract and so was virus-triggered pro-inflammatory interleukin 6 secretion. Modern herbal monographs consider the usage of this medicinal plant as safe. Thus, the in vitro results reported here should encourage further research on the clinical relevance and applicability of the extract as prevention strategy for SARS-CoV-2 infection MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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