Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (732)

NSP5 (34)

ProteinN (30)

ProteinS1 (28)

ComplexRdRp (23)


SARS-CoV-2 Proteins
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    Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses

    Authors: Shuye Zhang

    doi:10.1101/2020.02.16.951913 Date: 2020-02-21 Source: bioRxiv

    The new coronavirus (2019-nCoV) outbreak from December 2019 in Wuhan, Hubei, China, has been declared a global public health emergency. Angiotensin I converting enzyme 2 HGNC ( ACE2 HGNC), is the host receptor by 2019-nCov to infect human cells. Although ACE2 HGNC is reported to be expressed in lung, liver, stomach, ileum, kidney and colon MESHD, its expressing levels are rather low, especially in the lung. 2019-nCoV may use co-receptors/auxiliary proteins as ACE2 HGNC partner to facilitate the virus entry. To identify the potential candidates, we explored the single cell gene expression atlas including 119 cell types of 13 human tissues and analyzed the single cell co-expression spectrum of 51 reported RNA virus receptors and 400 other membrane proteins. Consistent with other recent reports, we confirmed that ACE2 was mainly expressed in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules. Intriguingly, we found that the candidate co-receptors, manifesting the most similar expression patterns with ACE2 HGNC across 13 human tissues, are all peptidases, including ANPEP HGNC, DPP4 HGNC and ENPEP HGNC. Among them, ANPEP HGNC and DPP4 HGNC are the known receptors for human CoVs, suggesting ENPEP HGNC as another potential receptor for human CoVs. We also conducted "CellPhoneDB" analysis to understand the cell crosstalk between CoV-targets and their surrounding cells across different tissues. We found that macrophages frequently communicate with the CoVs targets through chemokine and phagocytosis signaling, highlighting the importance of tissue macrophages in immune defense and immune pathogenesis.

    Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV)

    Authors: Jiahua He; Huanyu Tao; Yumeng Yan; Sheng-You Huang; Yi Xiao

    doi:10.1101/2020.02.17.952903 Date: 2020-02-21 Source: bioRxiv

    Since December, 2019, an outbreak of pneumonia MESHD caused by the new coronavirus (2019-nCoV) has hit the city of Wuhan in the Hubei Province. With the continuous development of the epidemic, it has become a national public health crisis and calls for urgent antiviral treatments or vaccines. The spike protein PROTEIN on the coronavirus envelope is critical for host cell infection MESHD and virus vitality. Previous studies showed that 2019-nCoV is highly homologous to human SARS-CoV MESHD and attaches host cells though the binding of the spike receptor binding domain (RBD) domain to the angiotensin-converting enzyme II ( ACE2 HGNC). However, the molecular mechanisms of 2019-nCoV binding to human ACE2 HGNC and evolution of 2019-nCoV remain unclear. In this study, we have extensively studied the RBD- ACE2 HGNC complex, spike protein PROTEIN, and free RBD systems of 2019-nCoV and SARS-CoV MESHD using protein-protein docking and molecular dynamics (MD) simulations. It was shown that the RBD- ACE2 HGNC binding free energy for 2019-nCoV is significantly lower than that for SARS-CoV MESHD, which is consistent with the fact that 2019-nCoV is much more infectious than SARS-CoV MESHD. In addition, the spike protein PROTEIN of 2019-nCoV shows a significantly lower free energy than that of SARS-CoV MESHD, suggesting that 2019-nCoV is more stable and able to survive a higher temperature than SARS-CoV MESHD. This may also provide insights into the evolution of 2019-nCoV because SARS-like coronaviruses are thought to have originated in bats that are known to have a higher body-temperature than humans. It was also revealed that the RBD of 2019-nCoV is much more flexible especially near the binding site and thus will have a higher entropy penalty upon binding ACE2 HGNC, compared to the RBD of SARS-CoV MESHD. That means that 2019-nCoV will be much more temperature-sensitive in terms of human infection than SARS-CoV MESHD. With the rising temperature, 2019-nCoV is expected to decrease its infection ability much faster than SARS-CoV MESHD, and get controlled more easily. The present findings are expected to be helpful for the disease prevention and control as well as drug and vaccine development of 2019-nCoV.

    A Multiscale and Comparative Model for Receptor Binding of 2019 Novel Coronavirus and the Implication of its Life Cycle in Host Cells

    Authors: Zhaoqian Su; Yinghao Wu

    doi:10.1101/2020.02.20.958272 Date: 2020-02-21 Source: bioRxiv

    The respiratory syndrome MESHD caused by a new type of coronavirus has been emerging from China and caused more than 1000 death globally since December 2019. This new virus, called 2019 novel coronavirus (2019-nCoV) uses the same receptor called Angiotensinconverting enzyme 2 ( ACE2 HGNC) to attack humans as the coronavirus that caused the severe acute respiratory syndrome MESHD (SARS) seventeen years ago. Both viruses recognize ACE2 HGNC through the spike proteins (S PROTEIN S-protein HGNC) on their surfaces. It was found that the S-protein PROTEIN S-protein HGNC from the SARS coronavirus ( SARS-CoV MESHD) bind stronger to ACE2 HGNC than 2019-nCoV. However, function of a bio-system is often under kinetic, rather than thermodynamic, control. To address this issue, we constructed a structural model for complex formed between ACE2 HGNC and the S-protein PROTEIN S-protein HGNC from 2019-nCoV, so that the rate of their association can be estimated and compared with the binding of S-protein HGNC S-protein PROTEIN from SARS-CoV MESHD by a multiscale simulation method. Our simulation results suggest that the association of new virus to the receptor is slower than SARS, which is consistent with the experimental data obtained very recently. We further integrated this difference of association rate between virus and receptor into a mathematical model which describes the life cycle of virus in host cells and its interplay with the innate immune system. Interestingly, we found that the slower association between virus and receptor can result in longer incubation period, while still maintaining a relatively higher level of viral concentration in human body. Our computational study therefore provides, from the molecular level, one possible explanation that the new disease by far spread much faster than SARS.

    Functional pangenome analysis provides insights into the origin, function and pathways to therapy of SARS-CoV-2 coronavirus

    Authors: Intikhab Alam; Allan K Kamau; Maxat Kulmanov; Stefan T Arold; Arnab T Pain; Takashi Gojobori; Carlos M. Duarte

    doi:10.1101/2020.02.17.952895 Date: 2020-02-21 Source: bioRxiv

    The spread of the novel coronavirus (SARS-CoV-2) has triggered a global emergency, that demands urgent solutions for detection and therapy to prevent escalating health, social and economic impacts. The spike protein (S PROTEIN) of this virus enables binding to the human receptor ACE2 HGNC, and hence presents a prime target for vaccines preventing viral entry into host cells1. The S proteins PROTEIN from SARS-CoV-1 and SARS-CoV-2 MESHD are similar2, but structural differences in the receptor binding domain (RBD) preclude the use of SARS-CoV-1-specific neutralizing antibodies to inhibit SARS-CoV-23. Here we used comparative pangenomic analysis of all sequenced Betacoronaviruses to reveal that, among all core gene clusters present in these viruses, the envelope protein E PROTEIN shows a variant shared by SARS and SARS-Cov2 with two completely-conserved key functional features, an ion-channel and a PDZ-binding Motif (PBM). These features trigger a cytokine storm that activates the inflammasome, leading to increased edema MESHD in lungs causing the acute respiratory distress syndrome MESHD ( ARDS MESHD)4-6, the leading cause of death MESHD in SARS-CoV-1 and SARS-CoV-2 infection7 MESHD SARS-CoV-2 infection MESHD7,8. However, three drugs approved for human use may inhibit SARS-CoV-1 and SARS-CoV-2 Protein E PROTEIN, either acting upon the ion channel (Amantadine and Hexamethylene amiloride9,10) or the PBM (SB2035805), thereby potentially increasing the survival of the host, as already demonstrated for SARS-CoV-1in animal models. Hence, blocking the SARS protein E PROTEIN inhibits development of ARDS in vivo. Given that our results demonstrate that the protein E PROTEIN subcluster for the SARS clade is quasi-identical for the key functional regions of SARS-CoV-1 and SARS-CoV-2, we conclude that use of approved drugs shown to act as SARS E protein PROTEIN inhibitors can help prevent further casualties from COVID-2019 while vaccines and other preventive measures are being developed.

    Structural basis for the recognition of the 2019-nCoV by human ACE2

    Authors: Renhong Yan; Yuanyuan Zhang; Yingying Guo; Lu Xia; Qiang Zhou

    doi:10.1101/2020.02.19.956946 Date: 2020-02-20 Source: bioRxiv

    Angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) has been suggested to be the cellular receptor for the new coronavirus (2019-nCoV) that is causing the coronavirus disease 2019 MESHD ( COVID-19 MESHD). Like other coronaviruses such as the SARS-CoV, the 2019-nCoV uses the receptor binding domain (RBD) of the surface spike glycoprotein PROTEIN ( S protein PROTEIN S protein HGNC) to engage ACE2 HGNC. We most recently determined the structure of the full-length human ACE2 HGNC in complex with a neutral amino acid transporter B0AT1 HGNC. Here we report the cryo-EM structure of the full-length human ACE2 HGNC bound to the RBD of the 2019-nCoV at an overall resolution of 2.9 [A] in the presence of B0AT1 HGNC. The local resolution at the ACE2 HGNC-RBD interface is 3.5 [A], allowing analysis of the detailed interactions between the RBD and the receptor. Similar to that for the SARS-CoV MESHD, the RBD of the 2019-nCoV is recognized by the extracellular peptidase domain (PD) of ACE2 HGNC mainly through polar residues. Pairwise comparison reveals a number of variations that may determine the different affinities between ACE2 HGNC and the RBDs from these two related viruses.

    SARS-CoV- 2 and SARS-CoV Spike PROTEIN-RBD Structure and Receptor Binding Comparison and Potential Implications on Neutralizing Antibody and Vaccine Development

    Authors: Liangzhi Xie; Chunyun Sun; Chunxia Luo; Yanjing Zhang; Jie Zhang; Jiahui Yang; Long Chen; Ji Yang; Jing Li

    doi:10.1101/2020.02.16.951723 Date: 2020-02-20 Source: bioRxiv

    SARS-CoV-2 and SARS-CoV MESHD share a common human receptor ACE2 HGNC. Protein-protein interaction structure modeling indicates that spike-RBD of the two viruses also has similar overall binding conformation and binding free energy to ACE2 HGNC. In vitro assays using recombinant ACE2 HGNC proteins and ACE2 HGNC expressing cells confirmed the two coronaviruses similar binding affinities to ACE2 HGNC. The above studies provide experimental supporting evidences and possible explanation for the high transmissibility observed in the SARS-CoV-2 outbreak. Potent ACE2 HGNC-blocking SARS-CoV neutralizing antibodies showed limited cross-binding and neutralizing activities to SARS-CoV-2. ACE2 HGNC-non-blocking SARS-CoV RBD MESHD antibodies, though with weaker neutralizing activities against SARS-CoV MESHD, showed positive cross-neutralizing activities to SARS-CoV-2 with an unknown mechanism. These findings suggest a trade-off between the efficacy and spectrum for therapeutic antibodies to different coronaviruses, and hence highlight the possibilities and challenges in developing broadly protecting antibodies and vaccines against SARS-CoV-2 and its future mutants.

    Crystal structure of the 2019-nCoV spike receptor-binding domain bound with the ACE2 HGNC receptor

    Authors: Jun Lan; Jiwan Ge; Jinfang Yu; Sisi Shan; Huan Zhou; Shilong Fan; Qi Zhang; Xuanling Shi; Qisheng Wang; Linqi Zhang; Xinquan Wang

    doi:10.1101/2020.02.19.956235 Date: 2020-02-20 Source: bioRxiv

    A novel and highly pathogenic coronavirus (2019-nCoV) has caused an outbreak in Wuhan city, Hubei province of China since December 2019, and soon spread nationwide and spilled over to other countries around the world. To better understand the initial step of infection at atomic-level, we determined the crystal structure of the 2019-nCoV spike receptor-binding domain (RBD) bound with the cell receptor ACE2 HGNC at 2.45 [A] resolution. The overall ACE2 HGNC-binding mode of the 2019-nCoV RBD is nearly identical to that of the SARS-CoV RBD MESHD, which also utilizes ACE2 HGNC as the cell receptor. Structural analysis identified residues in 2019-nCoV RBD critical for ACE2 HGNC binding, and majority of which are either highly conserved or shared similar side chain properties with those in the SARS-CoV RBD MESHD. Such similarity in structure and sequence strongly argue for a convergent evolution between 2019-nCoV and SARS-CoV RBD MESHD for improved binding to ACE2 HGNC despite of being segregated in different genetic lineages in the betacoronavirus genus. The epitopes of two SARS-CoV antibodies targeting the RBD are also analyzed with the 2019-nCoV RBD, providing insights into future identification of cross-reactive antibodies.

    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.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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