Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (99)

ProteinN (5)

ProteinE (3)

NSP5 (2)

ComplexRdRp (1)


SARS-CoV-2 Proteins
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    A single-cell RNA expression map of coronavirus receptors and associated factors in developing human embryos

    Authors: Stacy Colaco; Karisma Chhabria; Domdatt Singh; Anshul Bhide; Neha Singh; Abhishek Singh; Atahar Husein; Anuradha Mishra; Richa Sharma; Nancy Ashary; Deepak Modi

    id:2004.04935v2 Date: 2020-04-10 Source: arXiv

    To predict if developing human embryos are permissive to coronaviruses, we analyzed publicly available single cell RNA-seq datasets of zygotes, 4-cell, 8-cell, morula, inner cell mass, epiblast, primitive endoderm and trophectoderm for the coronavirus receptors ( ACE2 HGNC, BSG HGNC, DPP4 HGNC and ANPEP HGNC), the Spike protein PROTEIN cleavage enzymes ( TMPRSS2 HGNC, CTSL HGNC). We also analyzed the presence of host genes involved in viral replication, the endosomal sorting complexes required for transport (ESCRT) and SARS-Cov-2 interactions. The results reveal that ACE2 HGNC, BSG HGNC, DPP4 HGNC and ANPEP HGNC are expressed in the cells of the zygote, to blastocyst including the trophectodermal lineage. ACE2 HGNC, TMPRSS, BSG HGNC and CTSL HGNC are co-transcribed in a proportion of epiblast cells and most cells of the trophectoderm. The embryonic and trophectodermal cells also express genes for proteins ESCRT, viral replication and those that interact with SARS-CoV-2. We identified 1985 genes in epiblast and 1452 genes in the trophectoderm that are enriched in the ACE2 HGNC and TMPRSS2 HGNC co-expressing cells; 216 genes of these are common in both the cell types. These genes are associated with lipid metabolism, lysosome, peroxisome and oxidative phosphorylation pathways. Together our results suggest that developing human embryos could be permissive to coronavirus entry by both canonical and non-canonical mechanisms and they also express the genes for proteins involved in viral endocytosis and replication. This knowledge will be useful for evidence-based patient management for IVF during the COVID-19 pandemic MESHD COVID-19 pandemic MESHD.

    Implications of the virus-encoded miRNA and host miRNA in the pathogenicity of SARS-CoV-2

    Authors: Zhi Liu; Jianwei Wang; Yuyu Xu; Mengchen Guo; Kai Mi; Rui Xu; Yang Pei; Qiangkun Zhang; Xiaoting Luan; Zhibin Hu; Xingyin Liu#

    id:2004.04874v1 Date: 2020-04-10 Source: arXiv

    The outbreak of COVID-19 MESHD caused by SARS-CoV-2 has rapidly spread worldwide and has caused over 1,400,000 infections and 80,000 deaths. There are currently no drugs or vaccines with proven efficacy for its prevention and little knowledge was known about the pathogenicity mechanism of SARS-CoV-2 infection MESHD. Previous studies showed both virus and host-derived MicroRNAs (miRNAs) played crucial roles in the pathology of virus infection MESHD. In this study, we use computational approaches to scan the SARS-CoV-2 genome for putative miRNAs and predict the virus miRNA targets on virus and human genome as well as the host miRNAs targets on virus genome. Furthermore, we explore miRNAs involved dysregulation MESHD caused by the virus infection MESHD. Our results implicated that the immune response and cytoskeleton organization are two of the most notable biological processes regulated by the infection-modulated miRNAs. Impressively, we found hsa-miR-4661-3p was predicted to target the S gene of SARS-CoV-2, and a virus-encoded miRNA MR147-3p could enhance the expression of TMPRSS2 HGNC with the function of strengthening SARS-CoV-2 infection MESHD in the gut. The study may provide important clues for the mechisms of pathogenesis of SARS-CoV-2.

    Single-cell atlas of a non-human primate reveals new pathogenic mechanisms of COVID-19 MESHD

    Authors: Lei Han; Xiaoyu Wei; Chuanyu Liu; Giacomo Volpe; Zhifeng Wang; Taotao Pan; Yue Yuan; Ying Lei; Yiwei Lai; Carl Ward; Yeya Yu; Mingyue Wang; Quan Shi; Tao Wu; Liang Wu; Ya Liu; Chunqing Wang; Yuanhang Zhang; Haixi Sun; Hao Yu; Zhenkun Zhuang; Tingting Tang; Yunting Huang; Haorong Lu; Liqin Xu; Jiangshan Xu; Mengnan Cheng; Yang Liu; Chi Wai Wong; Tao Tan; Weizhi Ji; Patrick H. Maxwell; Huanming Yang; Jian Wang; Shida Zhu; Shiping Liu; Xun Xu; Yong Hou; Miguel A. Esteban; Longqi Liu

    doi:10.1101/2020.04.10.022103 Date: 2020-04-10 Source: bioRxiv

    Stopping COVID-19 MESHD is a priority worldwide. Understanding which cell types are targeted by SARS-CoV-2 virus, whether interspecies differences exist, and how variations in cell state influence viral entry is fundamental for accelerating therapeutic and preventative approaches. In this endeavor, we profiled the transcriptome of nine tissues from a Macaca fascicularis monkey at single-cell resolution. The distribution of SARS-CoV-2 facilitators, ACE2 HGNC and TMRPSS2, in different cell subtypes showed substantial heterogeneity across lung, kidney, and liver. Through co-expression analysis, we identified immunomodulatory proteins such as IDO2 HGNC and ANPEP HGNC as potential SARS-CoV-2 targets responsible for immune cell exhaustion. Furthermore, single-cell chromatin accessibility analysis of the kidney unveiled a plausible link between IL6-mediated innate immune responses aiming to protect tissue and enhanced ACE2 HGNC expression that could promote viral entry. Our work constitutes a unique resource for understanding the physiology and pathophysiology of two phylogenetically close species, which might guide in the development of therapeutic approaches in humans. Bullet pointsO_LIWe generated a single-cell transcriptome atlas of 9 monkey tissues to study COVID-19 MESHD. C_LIO_LIACE2+ TMPRSS2 HGNC+ epithelial cells of lung, kidney and liver are targets for SARS-CoV-2. C_LIO_LIACE2 correlation analysis shows IDO2 HGNC and ANPEP HGNC as potential therapeutic opportunities. C_LIO_LIWe unveil a link between IL6, STAT transcription factors and boosted SARS-CoV-2 entry. C_LI

    Gene expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue

    Authors: Jennifer A Aguiar; Benjamin Jean-Marie Tremblay; Michael J Mansfield; Owen Woody; Briallen Lobb; Arinjay Banerjee; Abiram Chandiramohan; Nicholas Tiessen; Anna Dvorkin-Gheva; Spencer Revill; Matthew S Miller; Christopher Carlsten; Louise Organ; Chitra Joseph; Alison John; Paul J Hanson; Bruce M McManus; Gisli Jenkins; Karen Mossman; Kjetil Ask; Andrew C Doxey; Jeremy A Hirota

    doi:10.1101/2020.04.07.030742 Date: 2020-04-09 Source: bioRxiv

    In December 2019, SARS-CoV-2 emerged causing the COVID-19 MESHD COVID-19 MESHD pandemic. SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilizes ACE2 HGNC and TMPRSS2 HGNC host molecules for viral entry. ACE2 HGNC and TMPRSS2 HGNC have recently been implicated in SARS-CoV-2 viral infection MESHD. Additional host molecules including ADAM17 HGNC, cathepsin L HGNC, CD147 HGNC, and GRP78 HGNC may also function as receptors for SARS-CoV-2. To determine the expression and in situ localization of candidate SARS-CoV-2 receptors in the respiratory mucosa, we analyzed gene expression datasets from airway epithelial cells of 515 healthy subjects, gene promoter activity analysis using the FANTOM5 dataset containing 120 distinct sample types, single cell RNA sequencing (scRNAseq) of 10 healthy subjects, immunoblots on multiple airway epithelial cell types, and immunohistochemistry on 98 human lung samples. We demonstrate absent to low ACE2 HGNC promoter activity in a variety of lung epithelial cell samples and low ACE2 HGNC gene expression in both microarray and scRNAseq datasets of epithelial cell populations. Consistent with gene expression, rare ACE2 HGNC protein expression was observed in the airway epithelium and alveoli of human lung. We present confirmatory evidence for the presence of TMPRSS2 HGNC, CD147 HGNC, and GRP78 HGNC protein in vitro in airway epithelial cells and confirm broad in situ protein expression of CD147 HGNC in the respiratory mucosa. Collectively, our data suggest the presence of a mechanism dynamically regulating ACE2 HGNC expression in human lung, perhaps in periods of SARS-CoV-2 infection MESHD, and also suggest that alternate receptors for SARS-CoV-2 exist to facilitate initial host cell infection.

    An Oral Live Attenuated Vaccine Strategy against Severe Acute Respiratory Syndrome Coronavirus 2 (2019-nCoV)

    Authors: Madhusudana Girija Sanal; Ravi Chandra Dubey

    id:10.20944/preprints202004.0153.v1 Date: 2020-04-09 Source:

    Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 HGNC ( ACE2 HGNC) and TMPRSS2 HGNC which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection MESHD because the attenuated virus initially infects MESHD the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.

    Relative Abundance of SARS-CoV-2 Entry Genes in the Enterocytes of the Lower Gastrointestinal Tract

    Authors: Jaewon J Lee; Scott Kopetz; Eduardo Vilar; John Paul Shen; Ken Chen; Anirban Maitra

    doi:10.1101/2020.04.08.033001 Date: 2020-04-09 Source: bioRxiv

    COVID-19 MESHD, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world and was declared a pandemic by the World Health Organization, thus leading to a rapid surge in the efforts to understand the mechanisms of transmission, methods of prevention, and potential therapies. While COVID-19 MESHD frequently manifests as a respiratory infection MESHD,1 there is evidence for infection of the gastrointestinal MESHD ( GI MESHD) tract1-4 with documented viral RNA shedding in the stool of infected MESHD patients.2,4 In this study, we aimed to investigate the expression of ACE2 HGNC and TMPRSS2 HGNC, which are required for SARS-CoV-2 entry into mammalian cells,5 from single-cell RNA sequencing (scRNA-seq) datasets of five different parts of the GI MESHD tract: esophagus, stomach, pancreas, small intestine, and colon MESHD/rectum.

    PolypharmDB, a Deep Learning-Based Resource, Quickly Identifies Repurposed Drug Candidates for COVID-19 MESHD

    Authors: Dar'ya S. Redka; Stephen S. MacKinnon; Melissa Landon; Andreas Windemuth; Naheed Kurji; Vijay Shahani

    doi:10.26434/chemrxiv.12071271.v1 Date: 2020-04-06 Source: ChemRxiv

    There is an immediate need to discover treatments for COVID-19 MESHD, the pandemic caused by the SARS-CoV-2 virus. Standard small molecule drug discovery workflows that start with library screens are an impractical path forward given the timelines to discover, develop, and test clinically. To accelerate the time to patient testing, here we explored the therapeutic potential of small molecule drugs that have been tested to some degree in a clinical environment, including approved medications, as possible therapeutic interventions for COVID-19 MESHD. Motivating our process is a concept termed polypharmacology, i.e. off-target interactions that may hold therapeutic potential. In this work, we used Ligand Design, our deep learning drug design platform, to interrogate the polypharmacological profiles of an internal collection of small molecule drugs with federal approval or going through clinical trials, with the goal of identifying molecules predicted to modulate targets relevant for COVID-19 MESHD treatment. Resulting from our efforts is PolypharmDB, a resource of drugs and their predicted binding of protein targets across the human proteome. Mining PolypharmDB yielded molecules predicted to interact with human and viral drug targets for COVID-19 MESHD, including host proteins linked to viral entry and proliferation and key viral proteins associated with the virus life-cycle. Further, we assembled a collection of prioritized approved drugs for two specific host-targets, TMPRSS2 HGNC and cathepsin B HGNC, whose joint inhibition was recently shown to block SARS-CoV-2 virus entry into host cells. Overall, we demonstrate that our approach facilitates rapid response, identifying 30 prioritized candidates for testing for their possible use as anti-COVID drugs. Using the PolypharmDB resource, it is possible to identify repurposed drug candidates for newly discovered targets within a single work day. We are making a complete list of the molecules we identified available at no cost to partners with the ability to test them for efficacy, in vitro and/or clinically.

    SARS-CoV-2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles

    Authors: Denisa Bojkova; Jake E McGreig; Katie-May McLaughlin; Stuart G Masterson; Marek Widera; Verena Kraehling; Sandra Ciesek; Mark N Wass; Martin Michaelis; Jindrich N Cinatl Jr.

    doi:10.1101/2020.04.03.024257 Date: 2020-04-05 Source: bioRxiv

    SARS-CoV-2 is a novel coronavirus currently causing a pandemic. We show that the majority of amino acid positions, which differ between SARS-CoV-2 and the closely related SARS-CoV MESHD, are differentially conserved suggesting differences in biological behaviour. In agreement, novel cell culture models revealed differences between the tropism of SARS-CoV-2 and SARS-CoV MESHD. Moreover, cellular ACE2 HGNC (SARS-CoV-2 receptor) and TMPRSS2 HGNC (enables virus entry via S protein PROTEIN cleavage) levels did not reliably indicate cell susceptibility to SARS-CoV-2. SARS-CoV-2 and SARS-CoV further differed in their drug sensitivity profiles. Thus, only drug testing using SARS-CoV-2 reliably identifies therapy candidates. Therapeutic concentrations of the approved protease inhibitor aprotinin displayed anti-SARS-CoV-2 activity. The efficacy of aprotinin and of remdesivir (currently under clinical investigation against SARS-CoV-2) were further enhanced by therapeutic concentrations of the proton pump inhibitor omeprazole (aprotinin 2.7-fold, remdesivir 10-fold). Hence, our study has also identified anti-SARS-CoV-2 therapy candidates that can be readily tested in patients.

    ACE2 HGNC and TMPRSS2 HGNC variants and expression as candidates to sex and country differences in COVID-19 MESHD severity in Italy

    Authors: Rosanna Asselta; Elvezia Maria Paraboschi; Alberto Mantovani; Stefano Duga

    doi:10.1101/2020.03.30.20047878 Date: 2020-04-02 Source: medRxiv

    Background: As the outbreak of coronavirus disease 2019 MESHD ( COVID-19 MESHD) progresses, prognostic markers for early identification of high-risk individuals are an urgent medical need. Italy has the highest rate of SARS-CoV-2 infection MESHD, the highest number of deaths, and the highest mortality rate among large countries. Worldwide, a more severe course of COVID-19 MESHD is associated with older age, comorbidities, and male sex. Hence, we searched for possible genetic components of the peculiar severity of COVID-19 MESHD among Italians, by looking at expression levels and variants in ACE2 HGNC and TMPRSS2 HGNC genes, which are crucial for viral infection. Methods: Exome and SNP array data from a large Italian cohort representative of the country's population were used to compare the burden of rare variants and the frequency of polymorphisms with European and East Asian populations. Moreover, we looked into gene expression databases to check for sex-unbalanced expression. Results: While we found no significant evidence that ACE2 HGNC is associated with disease severity/sex bias in the Italian population, TMPRSS2 HGNC levels and genetic variants proved to be possible candidate disease modulators, contributing to the observed epidemiological data among Italian patients. Conclusions: Our analysis suggests a role for TMPRSS2 HGNC variants and expression levels in modulating COVID-19 MESHD severity, a hypothesis that fosters a rapid experimental validation on large cohorts of patients with different clinical manifestations.

    SARS-CoV-2 receptor and entry genes are expressed by sustentacular cells in the human olfactory neuroepithelium

    Authors: Leon Fodoulian; Joel Tuberosa; Daniel Rossier; Madlaina Boillat; Chen-Da Kan; Veronique Pauli; Kristof Egervari; Johannes A. Lobrinus; Basile Landis; Alan Carleton; Ivan Rodriguez

    doi:10.1101/2020.03.31.013268 Date: 2020-04-02 Source: bioRxiv

    Various reports indicate an association between COVID-19 MESHD and anosmia MESHD, suggesting an infection of the olfactory sensory epithelium, and thus a possible direct virus access to the brain. To test this hypothesis, we generated RNA-seq libraries from human olfactory neuroepithelia MESHD, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 ( ACE2 HGNC), and for the virus internalization enhancer TMPRSS2 HGNC. We analyzed a human olfactory single-cell RNA-seq dataset and determined that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express ACE2 HGNC and TMPRSS2 HGNC. We then observed that the ACE2 HGNC protein was highly expressed in a subset of sustentacular cells in human and mouse olfactory tissues. Finally, we found ACE2 transcripts in specific brain cell types, both in mice and humans. Sustentacular cells thus represent a potential entry door for SARS-CoV-2 in a neuronal sensory system that is in direct connection with the brain.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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