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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (720)

ProteinN (158)

NSP5 (76)

ComplexRdRp (47)

ProteinE (44)


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SARS-CoV-2 Proteins
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    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.

    Potential T-cell and B-cell Epitopes of 2019-nCoV

    Authors: Ethan Fast; Russ B Altman; Binbin Chen

    doi:10.1101/2020.02.19.955484 Date: 2020-02-21 Source: bioRxiv

    As of early March, 2019-nCoV has infected more than one hundred thousand people and claimed thousands of lives. 2019-nCoV is a novel form of coronavirus that causes COVID-19 MESHD and has high similarity with SARS-CoV MESHD. No approved vaccine yet exists for any form of coronavirus. Here we use computational tools from structural biology and machine learning to identify 2019-nCoV T-cell and B-cell epitopes based on viral protein antigen presentation and antibody binding properties. These epitopes can be used to develop more effective vaccines and identify neutralizing antibodies. We identified 405 viral peptides with good antigen presentation scores for both human MHC-I and MHC-II alleles, and two potential neutralizing B-cell epitopes near the 2019-nCoV spike protein PROTEIN receptor binding domain (440-460 and 494-506). Analyzing mutation profiles of 68 viral genomes from four continents, we identified 96 coding-change mutations. These mutations are more likely to occur in regions with good MHC-I presentation scores (p=0.02). No mutations are present near the spike protein PROTEIN receptor binding domain. Based on these findings, the spike protein PROTEIN is likely immunogenic and a potential vaccine candidate. We validated our computational pipeline with SARS-CoV MESHD experimental data. Significance StatementThe novel coronavirus 2019-nCoV has affected more than 100 countries and continues to spread. There is an immediate need for effective vaccines that contain antigens which trigger responses from human T-cells and B-cells (known as epitopes). Here we identify potential T-cell epitopes through an analysis of human antigen presentation, as well as B-cell epitopes through an analysis of protein structure. We identify a list of top candidates, including an epitope located on 2019-nCoV spike protein PROTEIN that potentially triggers both T-cell and B-cell responses. Analyzing 68 samples, we observe that viral mutations are more likely to happen in regions with strong antigen presentation, a potential form of immune evasion. Our computational pipeline is validated with experimental data from SARS-CoV.

    scRNA-seq Profiling of Human Testes Reveals the Presence of ACE2 HGNC Receptor, a Target for SARS-CoV-2 Infection MESHD, in Spermatogonia, Leydig and Sertoli Cells

    Authors: Zhengpin Wang; Xiaojiang Xu

    id:10.20944/preprints202002.0299.v1 Date: 2020-02-21 Source: Preprints.org

    In December 2019, a novel coronavirus (SARS-CoV-2) was identified in patients with pneumonia MESHD (called COVID-19 MESHD) in Wuhan, Hubei Province, China. SARS-CoV-2 shares high sequence similarity and uses the same cell entry receptor, angiotensin-converting enzyme 2 ( ACE2 HGNC), as does severe acute respiratory syndrome coronavirus (SARS-CoV) MESHD. Several studies have provided bioinformatic evidence of potential routes for SARS-CoV-2 infection MESHD in respiratory, cardiovascular, digestive and urinary systems. However, whether the reproductive system is a potential target of SARS-CoV-2 infection MESHD has not been determined. Here, we investigate the expression pattern of ACE2 HGNC in adult human testis at the level of single-cell transcriptomes. The results indicate that ACE2 HGNC is predominantly enriched in spermatogonia, Leydig and Sertoli cells. Gene ontology analyses indicate that GO categories associated with viral reproduction and transmission are highly enriched in ACE2 HGNC-positive spermatogonia while male gamete generation related terms are down-regulated. Cell-cell junction and immunity related GO terms are increased in ACE2 HGNC-positive Leydig and Sertoli cells, but mitochondria and reproduction related GO terms are decreased. These findings provide evidence that human testes are a potential target of SARS-CoV-2 infection MESHD which may have significant impact on our understanding of the pathophysiology of this rapidly spreading disease.

    Epidemic analysis of COVID-19 MESHD in China after Wuhan was restricted

    Authors: anfeng yu; zhiwei wang; wei ren; zhiyong wu; zhipeng hu; luocheng li; yongle ruan; rui hu; feng shi

    doi:10.21203/rs.2.24289/v1 Date: 2020-02-21 Source: ResearchSquare

    BackgroundIn December 2019, Coronavirus Disease 2019 MESHD( COVID-19 MESHD) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection MESHD appeared in Wuhan, Hubei Province, China. The disease is highly infectious. Wuhan, Hubei Province decided restrict personnel movement on January 23.We analyze relevant data to show the situation of the COVID-19 MESHD epidemic in China.MethodsThe data was classified according to Hubei group, non-Hubei group, Hong Kong, Macao and Taiwan group, and Chinese Mainland group, and analyze the current situation and trend of the epidemic.ResultsThere was an explosive growth in the early stage of the epidemic. The epidemic situation began to improve in about two weeks after Wuhan was restricted,and the situation in non-Hubei was significantly better than that in Hubei.ConclusionThe blockade of Wuhan was a correct decision, cut off the outflow of tinfection sources, and the epidemic situation in all places turned around after the incubation period.

    Mucin 4 Protects Female Mice from Coronavirus Pathogenesis

    Authors: Jessica A Plante; Kenneth Plante; Lisa Gralinski; Anne Beall; Martin T. Ferris; Daniel Bottomly; Richard R Green; Shannon McWeeney; Mark T. Heise; Ralph S. Baric; Vineet D. Menachery

    doi:10.1101/2020.02.19.957118 Date: 2020-02-20 Source: bioRxiv

    Using incipient lines of the Collaborative Cross (CC), a murine genetic reference population, we previously identified a quantitative trait loci (QTL) associated with low SARS-CoV titer MESHD. In this study, we integrated sequence information and RNA expression of genes within the QTL to identify mucin 4 (Muc4) as a high priority candidate for controlling SARS-CoV titer MESHD in the lung. To test this hypothesis, we infected Muc4-/- mice and found that female, but not male, Muc4-/- mice developed more weight loss and disease MESHD following infection with SARS-CoV MESHD. Female Muc4-/- mice also had more difficulty breathing despite reduced lung pathology; however, no change in viral titers was observed. Comparing across viral families, studies with chikungunya virus, a mosquito-borne arthralgic virus, suggests that Muc4s impact on viral pathogenesis may be widespread. Although not confirming the original titer QTL, our data identifies a role for Muc4 in the SARS-CoV disease MESHD and viral pathogenesis. ImportanceGiven the recent emergence of SARS-CoV-2, this work suggest that Muc4 expression plays a protective role in female mice not conserved in male mice following SARS-CoV infection. With the SARS-CoV-2 outbreak continuing, treatments that modulate or enhance Muc4 activity may provide an avenue for treatment and improved outcomes. In addition, the work highlights the importance of studying host factors including host genetics and biological sex as key parameters influencing infection and disease outcomes.

    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.

    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.

    Multivariate Analyses of Codon Usage in 2019 Novel Coronavirus on the Genomic Landscape of Betacoronavirus

    Authors: Haogao Gu; Daniel K W Chu; Joseph Sriyal Malik Peiris; Leo L M Poon

    doi:10.1101/2020.02.15.950568 Date: 2020-02-20 Source: bioRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is a global health concern as it continues to spread within China and beyond. The causative agent of this disease, severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), belongs to the genus Betacoronavirus which also includes severe acute respiratory syndrome MESHD related coronavirus (SARSr-CoV) and Middle East respiratory syndrome MESHD related coronavirus (MERSr-CoV). Codon usage of viral genes are believed to be subjected to different selection pressures in different host environments. Previous studies on codon usage of influenza A viruses can help identify viral host origins and evolution trends, however, similar studies on coronaviruses are lacking. In this study, global correspondence analysis (CA), within-group correspondence analysis (WCA) and between-group correspondence analysis (BCA) were performed among different genes in coronavirus viral sequences. The amino acid usage pattern of SARS-CoV-2 was generally found similar to bat and human SARSr-CoVs. However, we found greater synonymous codon usage differences between SARS-CoV-2 and its phylogenetic relatives on spike and membrane genes, suggesting these two genes of SARS-CoV-2 are subjected to different evolutionary pressures.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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