Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (2227)

ProteinN (199)

NSP5 (65)

ProteinS1 (58)

ComplexRdRp (52)


SARS-CoV-2 Proteins
    displaying 2171 - 2180 records in total 2227
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    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.

    Revealing the Potency of Citrus and Galangal Constituents to Halt SARS-CoV-2 Infection MESHD

    Authors: Rohmad Yudi Utomo; Muthi' Ikawati; Edy Meiyanto

    id:10.20944/preprints202003.0214.v1 Date: 2020-03-12 Source:

    COVID-19 pandemic MESHD COVID-19 pandemic MESHD is a serious problem in the world today. The SARS-CoV-2 virus that causes COVID-19 MESHD has important proteins used for its infection and development, namely the protease and spike glycoprotein PROTEIN. The RBD (Receptor Binding Domain) of spike glycoprotein PROTEIN (RBD-S) can bind to the ACE2 (Angiotensin Converting Enzyme-2) receptor at the protease domain (PD) (PD-ACE2) of the host cell, thereby leading to a viral infection MESHD. This study aims to reveal the potential of compounds contained in Curcuma sp., Citrus sp., Alpinia galanga, and Caesalpinia sappan as anti SARS-CoV-2 through its binding to 3 protein receptors. The study was conducted by molecular docking using the MOE 2010 program (licensed from Faculty of Pharmacy UGM, Indonesia). The selected protein targets are RBD-S (PDB ID:6LXT), PD-ACE2 (PDB ID: 6VW1), and SARS-CoV-2 protease (PDB ID:6LU7). The affinities of bonds formed is represented as a docking score. The results show that hesperidin, one of the compounds in Citrus sp., has the lowest docking score for all three protein receptors representing the highest affinity to bind the receptors. Moreover, all of the citrus flavonoids possess good affinity to the respected receptors as well as curcumin, brazilin, and galangin, indicating that those compounds perform inhibitory potential for the viral infection MESHD and replication. In general, the results of this study indicate that Citrus sp. exhibit the best potential as an inhibitor to the development of the SARS-CoV-2, followed by galangal, sappan wood, and Curcuma sp. that can be consumed in daily life as prophylaxis of COVID-19 MESHD.

    The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 HGNC human receptor

    Authors: Esther S Brielle; Dina Schneidman; Michal Linial

    doi:10.1101/2020.03.10.986398 Date: 2020-03-12 Source: bioRxiv

    The COVID-19 MESHD disease has plagued over 110 countries and has resulted in over 4,000 deaths within 10 weeks. We compare the interaction between the human ACE2 HGNC receptor and the SARS-CoV-2 spike PROTEIN protein with that of other pathogenic coronaviruses using molecular dynamics simulations. SARS-CoV, SARS-CoV-2 MESHD, and HCoV-NL63 recognize ACE2 HGNC as the natural receptor but present a distinct binding interface to ACE2 HGNC and a different network of residue-residue contacts. SARS-CoV MESHD and SARS-CoV-2 have comparable binding affinities achieved by balancing energetics and dynamics. The SARS-CoV-2- ACE2 HGNC complex contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations relative to SARS-CoV MESHD. These findings expose an exceptional evolutionary exploration exerted by coronaviruses toward host recognition. We postulate that the versatility of cell receptor binding strategies has immediate implications on therapeutic strategies. One Sentence SummaryMolecular dynamics simulations reveal a temporal dimension of coronaviruses interactions with the host receptor.

    Repurposing Therapeutics for COVID-19 MESHD: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein PROTEIN and Viral Spike Protein PROTEIN-Human ACE2 HGNC Interface

    Authors: Micholas Smith; Jeremy C. Smith

    doi:10.26434/chemrxiv.11871402.v4 Date: 2020-03-11 Source: ChemRxiv

    The novel Wuhan coronavirus (SARS-CoV-2) has been sequenced, and the virus shares substantial similarity with SARS-CoV MESHD. Here, using a computational model of the spike protein (S PROTEIN S-protein HGNC) of SARS-CoV-2 interacting with the human ACE2 HGNC receptor, we make use of the world's most powerful supercomputer, SUMMIT, to enact an ensemble docking virtual high-throughput screening campaign and identify small-molecules which bind to either the isolated Viral S-protein HGNC S-protein PROTEIN at its host receptor region or to the S protein PROTEIN-human ACE2 HGNC interface. We hypothesize the identified small-molecules may be repurposed to limit viral recognition of host cells and/or disrupt host-virus interactions. A ranked list of compounds is given that can be tested experimentally.

    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/ 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:

    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.

    In silico study of the spike protein PROTEIN from SARS-CoV-2 interaction with ACE2 HGNC: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism

    Authors: Houcemeddine Othman; Zied Bouslama; Jean-Tristan Brandenburg; Jorge da Rocha; Yosr Hamdi; Kais Ghedira; Najet-Srairi Abid; Scott Hazelhurst

    doi:10.1101/2020.03.04.976027 Date: 2020-03-07 Source: bioRxiv

    The spread of COVID-19 MESHD caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) is more likely to be the cell receptor through which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 HGNC protein. By calculating the binding energy score between RBD and ACE2 HGNC, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 MESHD outbreak. Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein PROTEIN RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 HGNC and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of genetic engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2 HGNC, on the complex formation with SARS-CoV-2 RBD MESHD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.

    Monoclonal antibodies for the S2 subunit of spike of SARS-CoV cross-react with the newly-emerged SARS-CoV-2

    Authors: Zhiqiang Zheng; Vanessa M. Monteil; Sebastian Maurer-Stroh; Chow Wenn Yew; Carol Leong; Suganya Cheyyatraivendran Arularasu; Vincent Tak Kwong Chow; Raymond Tzer Pin Lin; Ali Mirazimi; Wanjin Hong; Yee-Joo Tan

    doi:10.1101/2020.03.06.980037 Date: 2020-03-07 Source: bioRxiv

    The emergence of a novel coronavirus, SARS-CoV-2, at the end of 2019 has resulted in widespread human infections across the globe. While genetically distinct from SARS-CoV MESHD, the etiological agent that caused an outbreak of severe acute respiratory syndrome MESHD (SARS) in 2003, both coronaviruses exhibit receptor binding domain (RBD) conservation and utilize the same host cell receptor, angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC), for virus entry. Therefore, it will be important to test the cross-reactivity of antibodies that have been previously generated against the surface spike ( S) glycoprotein PROTEIN of SARS-CoV MESHD in order to aid research on the newly emerged SARS-CoV-2. Here, we show that an immunogenic domain in the S2 subunit of SARS-CoV S MESHD is highly conserved in multiple strains of SARS-CoV-2. Consistently, four murine monoclonal antibodies (mAbs) raised against this immunogenic SARS-CoV MESHD fragment were able to recognise the S protein PROTEIN of SARS-CoV-2 expressed in a mammalian cell line. Importantly, one of them (mAb 1A9) was demonstrated to detect S in SARS-CoV-2-infected MESHD cells. To our knowledge, this is the first study showing that mAbs targeting the S2 domain of SARS-CoV can cross-react with SARS-CoV-2 and this observation is consistent with the high sequence conservation in the S2 subunit. These cross-reactive mAbs may serve as tools useful for SARS-CoV-2 research as well as for the development of diagnostic assays for its associated coronavirus disease COVID-19 MESHD.

    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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