Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (689)

NSP5 (33)

ProteinN (29)

ProteinS1 (26)

ComplexRdRp (23)


SARS-CoV-2 Proteins
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    Structure, function and antigenicity of the SARS-CoV-2 spike PROTEIN glycoprotein

    Authors: Alexandra C Walls; Young-Jun Park; M. Alexandra Tortorici; Abigail Wall; Andrew T McGuire; David Veesler

    doi:10.1101/2020.02.19.956581 Date: 2020-02-20 Source: bioRxiv

    The recent emergence of a novel coronavirus associated with an ongoing outbreak of pneumonia MESHD (Covid-2019) resulted in infections of more than 72,000 people and claimed over 1,800 lives. Coronavirus spike ( S) glycoprotein PROTEIN trimers promote entry into cells and are the main target of the humoral immune response. We show here that SARS-CoV-2 S mediates entry in VeroE6 cells and in BHK cells transiently transfected with human ACE2 HGNC, establishing ACE2 HGNC as a functional receptor for this novel coronavirus. We further demonstrate that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S MESHD bind with similar affinities to human ACE2 HGNC, which correlates with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein PROTEIN harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV MESHD and other SARS-related CoVs. We determined a cryo-electron microscopy structure of the SARS-CoV-2 S ectodomain trimer, demonstrating spontaneous opening of the receptor-binding domain, and providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S MESHD murine polyclonal sera potently inhibited SARS-CoV-2 S-mediated entry into target cells, thereby indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

    Pangolin homology associated with 2019-nCoV

    Authors: Zhigang Zhang; Qunfu Wu; Tao Zhang

    doi:10.1101/2020.02.19.950253 Date: 2020-02-20 Source: bioRxiv

    To explore potential intermediate host of a novel coronavirus is vital to rapidly control continuous COVID-19 MESHD spread. We found genomic and evolutionary evidences of the occurrence of 2019-nCoV-like coronavirus (named as Pangolin-CoV) from dead Malayan Pangolins. Pangolin-CoV is 91.02% and 90.55% identical at the whole genome level to 2019-nCoV and BatCoV RaTG13, respectively. Pangolin-CoV is the lowest common ancestor of 2019-nCoV and RaTG13. The S1 protein PROTEIN of Pangolin-CoV is much more closely related to 2019-nCoV than RaTG13. Five key amino-acid residues involved in the interaction with human ACE2 HGNC are completely consistent between Pangolin-CoV and 2019-nCoV but four amino-acid mutations occur in RaTG13. It indicates Pangolin-CoV has similar pathogenic potential to 2019-nCoV, and would be helpful to trace the origin and probable intermediate host of 2019-nCoV.

    Evidence for gastrointestinal infection of SARS-CoV-2

    Authors: Fei Xiao; Meiwen Tang; Xiaobin Zheng; Chunna Li; Jianzhong He; Zhongsi Hong; Siwen Huang; Zhenyi Zhang; Xianqi Lin; Zhaoxiong Fang; Renxu Lai; Shoudeng Chen; Jing Liu; Jin Huang; Jinyu Xia; Zhonghe Li; Guanmin Jiang; Ye Liu; Xiaofeng Li; Hong Shan

    doi:10.1101/2020.02.17.20023721 Date: 2020-02-20 Source: medRxiv

    The new coronavirus (SARS-CoV-2) outbreak originating from Wuhan, China, poses a threat to global health. While it's evident that the virus invades respiratory tract and transmits from human to human through airway, other viral tropisms and transmission routes remain unknown. We tested viral RNA in stool from 73 SARS-CoV-2-infected MESHD hospitalized patients using rRT-PCR. 53.42% of the patients tested positive in stool. 23.29% of the patients remained positive in feces even after the viral RNA decreased to undetectable level in respiratory tract. The viral RNA was also detected in gastrointestinal tissues. Furthermore, gastric, duodenal and rectal epithelia showed positive immunofluorescent staining of viral host receptor ACE2 HGNC and viral nucleocapsid protein PROTEIN in a case of SARS-CoV-2 infection MESHD. Our results provide evidence for gastrointestinal infection of SARS-CoV-2 MESHD, highlighting its potential fecal-oral transmission route.

    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.

    Single-cell Analysis of ACE2 HGNC Expression in Human Kidneys and Bladders Reveals a Potential Route of 2019-nCoV Infection MESHD

    Authors: Wei Lin; Longfei Hu; Yan Zhang; Jushua D. Ooi; Ting Meng; Peng Jin; Xiang Ding; Longkai Peng; Lei Song; Zhou Xiao; Xiang Ao; Xiangcheng Xiao; Qiaoling Zhou; Ping Xiao; Jue Fan; Yong Zhong

    doi:10.1101/2020.02.08.939892 Date: 2020-02-18 Source: bioRxiv

    Since December 2019, a novel coronavirus named 2019 coronavirus (2019-nCoV) has emerged in Wuhan of China and spread to several countries worldwide within just one month. Apart from fever MESHD and respiratory complications MESHD, acute kidney injury MESHD has been observed in some patients with 2019-nCoV. In a short period of time, angiotensin converting enzyme II ( ACE2 HGNC), have been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same for severe acute respiratory syndrome coronavirus MESHD (SARS). To investigate the possible cause of kidney damage MESHD in 2019-nCoV patients, we used both published kidney and bladder cell atlas data and an independent unpublished kidney single cell RNA-Seq data generated in-house to evaluate ACE2 HGNC gene expressions in all cell types in healthy kidneys and bladders. Our results showed the enriched expression of all subtypes of proximal tubule cells of kidney and low but detectable levels of expression in bladder epithelial cells. These results indicated the urinary system is a potential route for 2019-nCoV infection MESHD, along with the respiratory system and digestion system. Our findings suggested the kidney abnormalities of SARS and 2019-nCoV patients may be due to proximal tubule cells damage and subsequent systematic inflammatory response induced kidney injury. Beyond that, laboratory tests of viruses and related indicators in urine may be needed in some special patients of 2019-nCoV.

    Characterization of spike glycoprotein PROTEIN of 2019-nCoV on virus entry and its immune cross-reactivity with spike glycoprotein PROTEIN of SARS-CoV  

    Authors: Xiuyuan Ou; Yan Liu; Xiaobo Lei; Pei Li; Dan Mi; Lili Ren; Li Guo; Ting Chen; Jiaxing Hu; Zichun Xiang; Zhixia Mu; Xing Chen; Jieyong Chen; Keping Hu; Qi Jin; Jianwei Wang; Zhaohui Qian

    doi:10.21203/rs.2.24016/v1 Date: 2020-02-18 Source: ResearchSquare

    Since beginning of this century, there have already been three zoonotic outbreaks caused by beta coronaviruses (CoV), SA RS-CoV i MESHDn 2002-2003, MERS-CoV in 2012, and the newly identified 2019-nCoV in late 2019, Wuhan, China. As to Feb 10th, 2020, there are over 40,000 confirmed cases and over 900 deaths. However, little is known about the biology of this newly emerged virus. Here we developed a lentiviral based pseudovirus system for S protein PROTEIN of 2019-nCoV to study virus entry in BSL2 settings. First, we confirmed that human an giotensin converting enzyme 2 ( HGNChA CE2) HGNCis the main entry receptor for 2019-nCoV. Second, we found that 2019-nCoV S protein PROTEIN mediated entry on 293/hA CE2 c HGNCells was mainly through endocytosis, and PIKfyve, TP C2, HGNCand ca thepsin L a HGNCre critical for virus entry. Third, 2019-nCoV S protein PROTEIN is less stable than SARS-CoV, and it could trigger protease-independent and receptor dependent cell-cell fusion, which might help virus rapidly spread from cell to cell. Finally and more importantly, polyclonal anti-SARS S1 antibodies T62 effectively inhibited entry of SA RS-CoV S pseudovirions, MESHDbut almost had no effect on entry of 2019-nCoV S pseudovirions. Further studies using sera from one recovered SA RS-CoV p MESHDatient and five 2019-nCoV patients showed that there was only limited cross-neutralization activities between SA RS-CoV a MESHDnd 2019-nCoV sera, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for 2019-nCoV. 

    Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation

    Authors: Daniel Wrapp; Nianshuang Wang; Kizzmekia S Corbett; Jory A Goldsmith; Ching-Lin Hsieh; Olubukola Abiona; Barney S Graham; Jason S McLellan

    doi:10.1101/2020.02.11.944462 Date: 2020-02-15 Source: bioRxiv

    The outbreak of a novel betacoronavirus (2019-nCov) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike ( S) glycoprotein PROTEIN is a key target for urgently needed vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure ( MCM HGNC) development we determined a 3.5 [A]-resolution cryo-EM structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also show biophysical and structural evidence that the 2019-nCoV S binds ACE2 HGNC with higher affinity than SARS-CoV S MESHD. Additionally we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to nCoV-2019 S, suggesting antibody cross-reactivity may be limited between the two virus RBDs. The atomic-resolution structure of 2019-nCoV S should enable rapid development and evaluation of MCMs to address the ongoing public health crisis.

    Single-cell RNA expression profiling of ACE2 HGNC, the putative receptor of Wuhan 2019-nCoV, in the nasal tissue

    Authors: CHAO WU; Shufa Zheng; Yu Chen; Min Zheng

    doi:10.1101/2020.02.11.20022228 Date: 2020-02-13 Source: medRxiv

    A novel coronavirus (2019-nCoV) was first identified in Wuhan, Hubei Province, and then spreads to the other Provinces of China. WHO decides to determine a Public Health Emergency of International Concern (PHEIC) of 2019-nCoV. 2019-nCov was reported to share the same receptor, Angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC), with SARS-Cov. Here based on the public single-cell RNA-Seq datasets, we analyzed the ACE2 HGNC RNA expression profile in the tissues at different locations of the respiratory tract. The result indicates that the ACE2 HGNC expression appears in nasal epithelial cells. We found that the size of this population of ACE2 HGNC-expressing nasal epithelial cells is comparable with the size of the population of ACE2 HGNC-expression type II alveolar MESHD cells (AT2) in the Asian sample reported by Yu Zhao et al. We further detected 2019-nCoV by polymerase chain reaction (PCR) from the nasal-swab and throat-swab of seven suspected cases. We found that 2019-nCoV tends to have a higher concentration in the nasal-swab comparing to the throat-swab, which could attribute to the ACE2 HGNC-expressing nasal epithelial cells. We hope this study could be informative for virus-prevention strategy development, especially the treatment of nasal mucus.

    ACE2 HGNC Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection MESHD

    Authors: Caibin Fan; Kai Li; Yanhong Ding; Wei Lu Lu; Jianqing Wang

    doi:10.1101/2020.02.12.20022418 Date: 2020-02-13 Source: medRxiv

    In December 2019 and January 2020, novel coronavirus (2019-nCoV) - infected pneumonia MESHD (NCIP) occurred in Wuhan, and has already posed a serious threat to public health. ACE2 HGNC ( Angiotensin Converting Enzyme 2 HGNC) has been shown to be one of the major receptors that mediate the entry of 2019-nCoV into human cells, which also happens in severe acute respiratory syndrome coronavirus MESHD (SARS). Several researches have indicated that some patients have abnormal renal function MESHD or even kidney damage MESHD in addition to injury in respiratory system, and the related mechanism is unknown. This arouses our interest in whether coronavirus infection MESHD will affect the urinary and male reproductive systems. Here in this study, we used the online datasets to analyze ACE2 HGNC expression in different human organs. The results indicate that ACE2 HGNC highly expresses in renal tubular cells, Leydig cells and cells in seminiferous ducts in testis. Therefore, virus might directly bind to such ACE2 HGNC positive cells and damage the kidney and testicular tissue of patients. Our results indicate that renal function evaluation and special care should be performed in 2019-nCoV patients during clinical work, because of the kidney damage MESHD caused by virus and antiviral drugs with certain renal toxicity MESHD. In addition, due to the potential pathogenicity of the virus to testicular tissues, clinicians should pay attention to the risk of testicular lesions MESHD in patients during hospitalization and later clinical follow-up, especially the assessment and appropriate intervention in young patients' fertility.

    Diarrhea may be underestimated: a missing link in 2019 novel coronavirus

    Authors: Weicheng Liang; Zhijie Feng; Shitao Rao; Cuicui Xiao; Zexiao Lin; Qi Zhang; Wei Qi

    doi:10.1101/2020.02.03.20020289 Date: 2020-02-11 Source: medRxiv

    The outbreak of pneumonia MESHD caused by the 2019 Novel Coronavirus (2019-nCoV) was reported in Wuhan City, China. However, the clinical symptoms varied in different reports. Based on the results of inter-group difference test, we found that the incidence of diarrhea MESHD differed in three recent reports. As 2019-nCoV utilizes the same cell entry receptor ACE2 HGNC as severe acute respiratory syndrome coronavirus (SARS-CoV) MESHD and ACE2 HGNC tightly controls intestinal inflammation MESHD, to trace the route of infection mediated by 2019-nCoV, we used the single-cell RNA sequencing data for analysis. We found that the ACE2 HGNC mRNA was highly expressed in the healthy human small intestine rather than the lung. Besides, single-cell RNA sequencing data showed that ACE2 HGNC was significantly elevated in the proximal and distal enterocytes, where the small intestinal epithelium is exposed to the foreign pathogen. Thus, we suspect that ACE2 HGNC-expressing small intestinal epithelium cells might be vulnerable to 2019-nCoV infection MESHD when people eat infected wild animals and diarrhea MESHD may serve as an indicator for infection, suggesting that clinicians should pay more attention to patients with diarrhea MESHD during the outbreak of pneumonia MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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