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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (311)

ProteinN (25)

NSP5 (13)

ORF1ab (8)

ORF8 (5)


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SARS-CoV-2 Proteins
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    SARS-CoV-2, an evolutionary perspective of interaction with human ACE2 HGNC reveals undiscovered amino acids necessary for complex stability

    Authors: Vinicio Armijos-Jaramillo; Justin Yeager; Claire Muslin; Yunierkis Perez-Castillo

    doi:10.1101/2020.03.21.001933 Date: 2020-03-23 Source: bioRxiv

    The emergence of SARS-CoV-2 has resulted in more than 200,000 infections and nearly 9,000 deaths globally so far. This novel virus is thought to have originated from an animal reservoir, and acquired the ability to infect human cells using the SARS-CoV cell receptor hACE2 HGNC. In the wake of a global pandemic it is essential to improve our understanding of the evolutionary dynamics surrounding the origin and spread of a novel infectious disease MESHD. One way theory predicts selection pressures should shape viral evolution is to enhance binding with host cells. We first assessed evolutionary dynamics in select betacoronavirus spike protein PROTEIN genes to predict where these genomic regions are under directional or purifying selection between divergent viral lineages at various scales of relatedness. With this analysis, we determine a region inside the receptor-binding domain with putative sites under positive selection interspersed among highly conserved sites, which are implicated in structural stability of the viral spike protein PROTEIN and its union with human receptor hACE2 HGNC. Next, to gain further insights into factors associated with coronaviruses recognition of the human host receptor, we performed modeling studies of five different coronaviruses and their potential binding to hACE2 HGNC. Modeling results indicate that interfering with the salt bridges at hot spot 353 could be an effective strategy for inhibiting binding, and hence for the prevention of coronavirus infections MESHD. We also propose that a glycine residue at the receptor binding domain of the spike glycoprotein PROTEIN can have a critical role in permitting bat variants of the coronaviruses to infect human cells.

    Evaluation of Nucleocapsid and Spike Protein PROTEIN-based ELISAs for detecting antibodies against SARS-CoV-2

    Authors: Wanbing Liu; Lei Liu; Guomei Kou; Yaqiong Zheng; Yinjuan Ding; Wenxu Ni; Qiongshu Wang; Li Tan; Wanlei Wu; Shi Tang; Zhou Xiong; Shangen Zheng

    doi:10.1101/2020.03.16.20035014 Date: 2020-03-20 Source: medRxiv

    Background: At present, PCR-based nucleic acid detection cannot meet the demands for coronavirus infectious disease MESHD ( COVID-19 MESHD) diagnosis. Methods: 214 confirmed COVID-19 MESHD patients who were hospitalized in the General Hospital of Central Theater Command of the People's Liberation Army between January 18 and February 26, 2020, were recruited. Two Enzyme-Linked Immunosorbent Assay (ELISA) kits based on recombinant SARS-CoV-2 nucleocapsid protein PROTEIN (rN) and spike protein PROTEIN (rS) were used for detecting IgM and IgG antibodies, and their diagnostic feasibility was evaluated. Results: Among the 214 patients, 146 (68.2%) and 150 (70.1%) were successfully diagnosed with the rN-based IgM and IgG ELISAs, respectively; 165 (77.1%) and 159 (74.3%) were successfully diagnosed with the rS-based IgM and IgG ELISAs, respectively. The positive rates of the rN-based and rS-based ELISAs for antibody (IgM and/or IgG) detection were 80.4% and 82.2%, respectively. The sensitivity of the rS-based ELISA for IgM detection was significantly higher than that of the rN-based ELISA. We observed an increase in the positive rate for IgM and IgG with an increasing number of days post-disease onset (d.p.o.), but the positive rate of IgM dropped after 35 d.p.o. The positive rate of rN-based and rS-based IgM and IgG ELISAs was less than 60% during the early stage of the illness 0-10 d.p.o., and that of IgM and IgG was obviously increased after 10 d.p.o. Conclusions: ELISA has a high sensitivity, especially for the detection of serum samples from patients after 10 d.p.o, it can be an important supplementary method for COVID-19 MESHD diagnosis.

    Characterization of the SARS-CoV-2 Spike PROTEIN in an Early Prefusion Conformation

    Authors: Tingting Li; Qingbing Zheng; Hai Yu; Dinghui Wu; Wenhui Xue; Yuyun Zhang; Xiaofen Huang; Lizhi Zhou; Zhigang Zhang; Zhenghui Zha; Tingting Chen; Zhiping Wang; Jie Chen; Hui Sun; Tingting Deng; Yingbin Wang; Yixin Chen; Qinjian Zhao; Jun Zhang; Ying Gu; Shaowei Li; Ningshao Xia

    doi:10.1101/2020.03.16.994152 Date: 2020-03-17 Source: bioRxiv

    Pandemic coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) is caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there are no efficacious vaccines or therapeutics that are urgently needed. We expressed three versions of spike (S) proteins PROTEIN--receptor binding domain (RBD), S1 subunit and S ectodomain--in insect cells. RBD appears monomer in solutions, whereas S1 and S associate into homotrimer with substantial glycosylation. The three proteins confer excellent antigenicity with six convalescent COVID-19 MESHD patient sera. Cryo-electron microscopy (cryo-EM) analyses indicate that the SARS-CoV-2 S trimer dominate in a unique conformation distinguished from the classic prefusion conformation of coronaviruses by the upper S1 region at lower position ~15 [A] proximal to viral membrane. Such conformation is proposed as an early prefusion state for the SARS-CoV-2 spike PROTEIN that may broaden the knowledge of coronavirus and facilitate vaccine development.

    The sequence of human ACE2 HGNC is suboptimal for binding the S spike protein PROTEIN of SARS coronavirus 2

    Authors: Erik Procko

    doi:10.1101/2020.03.16.994236 Date: 2020-03-17 Source: bioRxiv

    The rapid and escalating spread of SARS coronavirus MESHD 2 (SARS-CoV-2) poses an immediate public health emergency. The viral spike protein S PROTEIN binds ACE2 HGNC on host cells to initiate molecular events that release the viral genome intracellularly. Soluble ACE2 HGNC inhibits entry of both SARS and SARS-2 coronaviruses by acting as a decoy for S binding sites, and is a candidate for therapeutic, prophylactic and diagnostic development. Using deep mutagenesis, variants of ACE2 HGNC are identified with increased binding to the receptor binding domain of S. Mutations are found across the interface, in the N90-glycosylation motif, and at buried sites where they are predicted to enhance local folding and presentation of the interaction epitope. When single substitutions are combined, large increases in binding can be achieved. The mutational landscape offers a blueprint for engineering high affinity proteins and peptides that block receptor binding sites on S to meet this unprecedented challenge.

    SARS-CoV-2 Entry Genes Are Most Highly Expressed in Nasal Goblet and Ciliated Cells within Human Airways

    Authors: Waradon Sungnak; Ni Huang; Christophe Bécavin; Marijn Berg; HCA Lung Biological Network

    id:2003.06122v1 Date: 2020-03-13 Source: arXiv

    The SARS-CoV-2 coronavirus, the etiologic agent responsible for COVID-19 MESHD coronavirus disease MESHD, is a global threat. To better understand viral tropism, we assessed the RNA expression of the coronavirus receptor, ACE2 HGNC, as well as the viral S protein PROTEIN priming protease TMPRSS2 HGNC thought to govern viral entry in single-cell RNA-sequencing (scRNA-seq) datasets from healthy individuals generated by the Human Cell Atlas consortium. We found that ACE2 HGNC, as well as the protease TMPRSS2 HGNC, are differentially expressed in respiratory and gut epithelial cells. In-depth analysis of epithelial cells in the respiratory tree reveals that nasal epithelial cells, specifically goblet/secretory cells and ciliated cells, display the highest ACE2 HGNC expression of all the epithelial cells analyzed. The skewed expression of viral receptors/entry-associated proteins towards the upper airway may be correlated with enhanced transmissivity. Finally, we showed that many of the top genes associated with ACE2 HGNC airway epithelial expression are innate immune-associated, antiviral genes, highly enriched in the nasal epithelial cells. This association with immune pathways might have clinical implications for the course of infection and viral pathology, and highlights the specific significance of nasal epithelia in viral infection MESHD. Our findings underscore the importance of the availability of the Human Cell Atlas as a reference dataset. In this instance, analysis of the compendium of data points to a particularly relevant role for nasal goblet and ciliated cells as early viral targets and potential reservoirs of SARS-CoV-2 infection MESHD. This, in turn, serves as a biological framework for dissecting viral transmission and developing clinical strategies for prevention and therapy.

    Inhibition of SARS-CoV-2 infection MESHD (previously 2019-nCoV) by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein PROTEIN that harbors a high capacity to mediate membrane fusion

    Authors: Shuai Xia; Meiqin Liu; Chao Wang; Wei Xu; Qiaoshuai Lan; Siliang Feng; Feifei Qi; Linlin Bao; Lanying Du; Shuwen Liu; Chuan Qin; Fei Sun; Zhengli Shi; Yun Zhu; Shibo Jiang; Lu Lu

    doi:10.1101/2020.03.09.983247 Date: 2020-03-12 Source: bioRxiv

    The recent outbreak of coronavirus disease MESHD ( COVID-19 MESHD) caused by SARS-CoV-2 infection MESHD in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection MESHD must first be confirmed. Therefore, we herein used a SARS-CoV-2 spike PROTEIN ( S) protein PROTEIN-mediated cell-cell fusion assay and found that SARS-CoV-2 showed plasma membrane fusion capacity superior to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in SARS-CoV-2 S MESHD S protein PROTEIN S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. We then generated a series of lipopeptides and found that the EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein PROTEIN-mediated membrane fusion and pseudovirus infection MESHD with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than that of EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, potently inhibiting replication of 4 live human coronaviruses, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by currently circulating SARS-CoV-2 and emerging SARSr-CoVs.

    Sequence variation of SARS-CoV-2 spike PROTEIN protein may facilitate stronger interaction with ACE2 HGNC promoting high infectivity

    Authors: Masaud Shah; Bilal Ahmad; Sangdun Choi; Hyun Goo Woo

    doi:10.21203/rs.3.rs-16932/v1 Date: 2020-03-09 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease MESHD ( COVID-19 MESHD), is a novel beta coronavirus emerged in China in 2019. Coronavirus uses spike glycoprotein PROTEIN to interact with host angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) and ensure cell recognition. High infectivity of SARS-CoV-2 raises questions on spike- ACE2 HGNC binding affinity and its neutralization by anti-SARS-CoV monoclonal antibodies (mAbs). Here, we observed Val-to-Lys417 mutation in the receptor-binding domains (RBD) of SARS-CoV-2, which established a Lys-Asp electrostatic interaction enhancing its ACE2 HGNC-binding. Pro-to-Ala475 substitution and Gly482 insertion in the AGSTPCNGV-loop of RBD hindered neutralization of SARS-CoV-2 by anti- SARS-CoV mAbs MESHD. In addition, we identified unique and structurally conserved conformational-epitopes on RBDs, which can be potential therapeutic targets. Collectively, we provide new insights into the mechanisms underlying the high infectivity of SARS-CoV-2 and development of new effective neutralizing agents.

    Medical Countermeasures Analysis of 2019-nCoV and Vaccine Risks for Antibody-Dependent Enhancement (ADE)

    Authors: Darrell O. Ricke; Robert W. Malone

    id:10.20944/preprints202003.0138.v1 Date: 2020-03-08 Source: Preprints.org

    Background: In 80% of patients, COVID-19 MESHD presents as mild disease1,2. 20% of cases develop severe (13%) or critical (6%) illness. More severe forms of COVID-19 MESHD present as clinical severe acute respiratory syndrome MESHD, but include a T-predominant lymphopenia3, high circulating levels of proinflammatory cytokines and chemokines, accumulation of neutrophils and macrophages in lungs, and immune dysregulation including immunosuppression4. Methods: All major SARS-CoV-2 proteins MESHD were characterized using an amino acid residue variation analysis method. Results predict that most SARS-CoV-2 proteins are evolutionary constrained, with the exception of the spike (S) protein PROTEIN extended outer surface. Results were interpreted based on known SARS-like coronavirus virology and pathophysiology, with a focus on medical countermeasure development implications. Findings: Non-neutralizing antibodies to variable S domains may enable an alternative infection pathway via Fc receptor-mediated uptake. This may be a gating event for the immune response dysregulation observed in more severe COVID-19 MESHD disease. Prior studies involving vaccine candidates for FCoV5,6 SARS-CoV-17-10 and Middle East Respiratory Syndrome coronavirus (MERS-CoV MESHD) 11 demonstrate vaccination-induced antibody-dependent enhancement of disease (ADE), including infection of phagocytic antigen presenting cells (APC). T effector cells are believed to play an important role in controlling coronavirus infection MESHD; pan-T depletion is present in severe COVID-19 MESHD disease3 and may be accelerated by APC infection MESHD. Sequence and structural conservation of S motifs suggests that SARS and MERS vaccine ADE risks may foreshadow SARS-CoV-2 S-based vaccine risks. Autophagy inhibitors may reduce APC infection MESHD and T-cell depletion12 13. Amino acid residue variation analysis identifies multiple constrained domains suitable as T cell vaccine targets. Evolutionary constraints on proven antiviral drug targets present in SARS-CoV-1 and SARS-CoV-2 may reduce risk of developing antiviral drug escape mutants. Interpretation: Safety testing of COVID-19 MESHD S protein PROTEIN-based B cell vaccines in animal models is strongly encouraged prior to clinical trials to reduce risk of ADE upon virus exposure.

    Cryo-electron microscopy structure of the SADS-CoV spike glycoprotein PROTEIN provides insights into an evolution of unique coronavirus spike proteins PROTEIN

    Authors: Songying Ouyang

    doi:10.1101/2020.03.04.976258 Date: 2020-03-07 Source: bioRxiv

    The current outbreak of Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) by a novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has aroused great public health concern. Coronavirus has a history of causing epidemics in human and animals. In 2017 an outbreak in piglets by a novel coronavirus was emerged designated as swine acute diarrhea syndrome coronavirus (SADS-CoV MESHD) which is originated from the same genus of horseshoe bats (Rhinolophus) as Severe Acute Respiratory Syndrome CoV (SARS-CoV MESHD) having a broad species tropism. In addition to human cells, it can also infect cell lines from diverse species. Coronavirus host range is determined by its spike glycoprotein PROTEIN (S). Given the importance of S protein PROTEIN in viral entry to cells and host immune responses, here we report the cryo-EM structure of the SADS-CoV S MESHD in the prefusion conformation at a resolution of 3.55 [A]. Our study reveals that SADS-CoV S MESHD structure takes an intra-subunit quaternary packing mode where the NTD HGNC and CTD from the same subunit pack together by facing each other. The comparison of NTD HGNC and CTD with that of the other four genera suggests the evolutionary process of the SADS-CoV S MESHD. Moreover, SADS-CoV S MESHD has several characteristic structural features, such as more compact architecture of S trimer, and masking of epitopes by glycan shielding, which may facilitate viral immune evasion. These data provide new insights into the evolutionary relationships of SADS-CoV S MESHD and would extend our understanding of structural and functional diversity, which will facilitate to vaccine development.

    LY6E impairs coronavirus fusion and confers immune control of viral disease

    Authors: Stephanie Pfaender; Katrina B Mar; Eleftherios Michailidis; Annika Kratzel; Dagny Hirt; Wenchun Fan; Nadine Ebert; Hanspeter Stalder; Hannah Kleine-Weber; Markus Hoffmann; H. Heinrich Hoffmann; Mohsan Saeed; Ronald Dijkman; Eike Steinmann; Mary Wight-Carter; Natasha W Hanners; Stefan Pohlmann; Tom Gallagher; Daniel Todt; Gert Zimmer; Charles M Rice; John W Schoggins; Volker Thiel

    doi:10.1101/2020.03.05.979260 Date: 2020-03-07 Source: bioRxiv

    Zoonotic coronaviruses (CoVs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Host immune responses to CoV are complex and regulated in part through antiviral interferons. However, the interferon-stimulated gene products that inhibit CoV are not well characterized2. Here, we show that interferon-inducible lymphocyte antigen 6 complex, locus E (LY6E) potently restricts cellular infection by multiple CoVs, including SARS-CoV, SARS-CoV-2 MESHD, and Middle East respiratory syndrome coronavirus (MERS-CoV) MESHD. Mechanistic studies revealed that LY6E inhibits CoV entry into cells by interfering with spike protein PROTEIN-mediated membrane fusion. Importantly, mice lacking Ly6e in hematopoietic cells were highly susceptible to murine CoV infection MESHD. Exacerbated viral pathogenesis in Ly6e knockout mice was accompanied by loss of hepatic and splenic immune cells and reduction in global antiviral gene pathways. Accordingly, we found that Ly6e directly protects primary B cells and dendritic cells from murine CoV infection MESHD. Our results demonstrate that LY6E is a critical antiviral immune effector that controls CoV infection MESHD and pathogenesis. These findings advance our understanding of immune-mediated control of CoV in vitro and in vivo, knowledge that could help inform strategies to combat infection by emerging CoV.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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