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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinE (148)

ProteinS (41)

ProteinN (33)

ComplexRdRp (18)

ProteinM (17)


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SARS-CoV-2 Proteins
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    Inhibition of PIKfyve kinase prevents infection by EBOV and SARS-CoV-2

    Authors: Yuan-Lin Kang; Yi-Ying Chou; Paul W Rothlauf; Zhuoming Liu; Timothy K Soh; David Cureton; James Brett Case; Rita E Chen; Michael S Diamond; Sean P.J. Whelan

    doi:10.1101/2020.04.21.053058 Date: 2020-04-21 Source: bioRxiv

    Virus entry is a multistep process. It initiates when the virus attaches to the host cell and ends when the viral contents reach the cytosol. Genetically unrelated viruses can subvert analogous subcellular mechanisms and use similar trafficking pathways for successful entry. Antiviral strategies targeting early steps of infection are therefore appealing, particularly when the probability for successful interference through a common step is highest. We describe here potent inhibitory effects on content release and infection by chimeric VSV containing the envelope proteins PROTEIN of Zaire ebolavirus (VSV-ZEBOV) or SARS-CoV-2 (VSV-SARS-CoV-2) elicited by Apilimod and Vacuolin-1, small molecule inhibitors of the main endosomal Phosphatidylinositol-3-Phosphate/Phosphatidylinositol 5-Kinase, PIKfyve. We also describe potent inhibition of SARS-CoV-2 strain 2019-nCoV/USA-WA1/2020 by Apilimod. These results define new tools for studying the intracellular trafficking of pathogens elicited by inhibition of PIKfyve kinase and suggest the potential for targeting this kinase in developing small-molecule antivirals against SARS-CoV-2.

    In-silico Immunomodelling of 2019-nCoV

    Authors: Amirhosein Maali; Hossein Teimouri; Shahin Amiri; Setare Adibzadeh; Mehdi Azad

    doi:10.21203/rs.3.rs-23657/v1 Date: 2020-04-17 Source: ResearchSquare

    Background: Novel Corona Virus 2019 (2019-nCoV) is a positive-sense single-strand RNA virus form coronaviridae family, responsible for corona virus infectious disease MESHD 2019 ( COVID-19 MESHD) with rapid transmission. The aim of this study is characterization of major viral proteins, prediction of antigen proteasomal cleavage pattern, MHC class I processing and presentation, B- and T-cell epitopes, and anti-inflammatory epitopes of 2019-nCoV, compared with SARS-CoV MESHD. Methods: The aminoacid sequence of spike surface ( S) glycoprotein PROTEIN, membrane (M) glycoprotein PROTEIN, envelop ( E) protein PROTEIN and nucleocapsid (N PROTEIN) phosphoprotein were obtained from NCBI. The sequences were aligned by MEGA 7.0 and modeled by SWISS-MODEL. The proteasomal cleavage pattern, MHC class I processing and T-cells epitopes were predicted via IEDB analysis and EPISOFT. The B-cell epitopes were predicted by BepiPred 2.0. Also, prediction of anti-inflammatory epitopes was performed by AntiFlam. Results: Two major antigen proteins, S PROTEIN glycoprotein and M glycoprotein of 2019-nCoV, respectively, have 26.57% and 20.59% less efficiency in proteasomal cleavage and presentation to MHC class I, comparing SARS-CoV MESHD. There are less B-cell predicted epitopes in 2019-nCoV, comparing SARS-CoV MESHD. The anti-inflammatory properties of 2019-nCoV S glycoprotein PROTEIN and N protein PROTEIN is higher than SARS-CoV MESHD. Discussion: It seems that the evolution of 2019-nCoV is on the way of deficiency in antigen presenting to MHC class I and escaping from cellular immunity. Also, the predicted hotspot epitopes potentially can be used to induction of adaptive cellular immunity against 2019-nCoV. In addition, 2019-nCoV appears to be less immunopathogenic than SARS-CoV MESHD due to its higher anti-inflammatory proteins.

    Genome based Evolutionary study of SARS-CoV-2 towards the Prediction of Epitope Based Chimeric Vaccine

    Authors: Mst Rubaiat Nazneen Akhand; Kazi Faizul Azim; Syeda Farjana Hoque; Mahmuda Akther Moli; Bijit Das Joy; Hafsa Akter; Ibrahim Khalil Afif; Nadim Ahmed; Mahmudul Hasan

    doi:10.1101/2020.04.15.036285 Date: 2020-04-15 Source: bioRxiv

    SARS-CoV-2 is known to infect the neurological MESHD, respiratory, enteric, and hepatic systems of human and has already become an unprecedented threat to global healthcare system. COVID-19 MESHD, the most serious public condition caused by SARS-CoV-2 leads the world to an uncertainty alongside thousands of regular death scenes. Unavailability of specific therapeutics or approved vaccine has made the recovery of COVI-19 more troublesome and challenging. The present in silico study aimed to predict a novel chimeric vaccines by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Conserved regions from the homologous protein sets of spike glycoprotein PROTEIN (S), membrane protein (M PROTEIN), envelope protein PROTEIN and nucleocapsid protein (N PROTEIN) were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins (S PROTEIN, E, M and N) reflected the close ancestral relation of SARS-CoV-2 to SARS-COV-1 and bat coronavirus. Numerous immunogenic epitopes (both T cell and B cell) were generated from the common fragments which were further ranked on the basis of antigenicity, transmembrane topology, conservancy level, toxicity MESHD and allergenicity pattern and population coverage analysis. Top putative epitopes were combined with appropriate adjuvants and linkers to construct a novel multiepitope subunit vaccine against COVID-19 MESHD. The designed constructs were characterized based on physicochemical properties, allergenicity, antigenicity and solubility which revealed the superiority of construct V3 in terms safety and efficacy. Essential molecular dynamics and Normal Mode analysis confirmed minimal deformability of the refined model at molecular level. In addition, disulfide engineering was investigated to accelerate the stability of the protein. Molecular docking study ensured high binding affinity between construct V3 and HLA cells, as well as with different host receptors. Microbial expression and translational efficacy of the constructs were checked using pET28a(+) vector of E. coli strain K12. The development of preventive measures to combat COVID-19 MESHD infections might be aided the present study. However, the in vivo and in vitro validation might be ensured with wet lab trials using model animals for the implementation of the presented data.

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) envelope (E) protein PROTEIN harbors a conserved BH3-like motif

    Authors: Vincent Navratil; Sonia Longhi; Marie Hardwick; Christophe Combet

    doi:10.1101/2020.04.09.033522 Date: 2020-04-10 Source: bioRxiv

    Disclaimer textThe authors have withdrawn their manuscript whilst they perform additional experiments to test some of their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

    The multi-epitope vaccine prediction to combat Pandemic SARS-CoV-2, an immunoinformatic approach

    Authors: K. M. Kaderi Kibria; Md. Shaid bin Islam; Hedayet Ullah; Mojnu Miah

    doi:10.21203/rs.3.rs-21853/v1 Date: 2020-04-07 Source: ResearchSquare

    Novel coronavirus (SARS-CoV-2) leads to coronavirus disease MESHD 19 ( COVID-19 MESHD) recently declared as a pandemic for its outbreak within almost 190 countries worldwide. No effective drugs and/or vaccines authenticated against this rapidly spreading virus till now. This study aims to establish an efficient multi-epitope vaccine that could elicit both T-cell and B-cell responses sufficient to recognize confirmed surface proteins of the virus. The sequences of the viral surface proteins, e PROTEIN.g. envelope protein (E PROTEIN), membrane glycoprotein (M PROTEIN), and S1 and S2 domain of spike surface glycoprotein (S PROTEIN) collected from the NCBI database. We adopted an immunoinformatic strategy to identify the immunogenic region of the proteins and assessed their affinity with MHC class-I and MHC class-II by various bioinformatics tools. Top epitopes have been selected and assessed for population coverage and conservancy among 180 SARS-CoV-2 genomes. Along with the above analyses, and results of Antigenicity, Allergenicity, and transmembrane location prediction, we selected top epitopes from these four proteins. The epitopes were assembled by the AAY linker to form a multi-epitope vaccine is 70 aa long, can be synthesized commercially. This should be processed by Antigen-presenting cells; consequently, the surface proteins might be recognized by the helper and cytotoxic T-cells as well as by B-cells. We also assessed the structural and various physicochemical properties of the novel chimeric peptide for its suitability as a multi-epitope vaccine. This in-silico study leads to a rationally designed potential vaccine candidate that could be assessed by wet-lab experiments driving towards efficient combat of the novel coronavirus outbreak.

    Coronavirus hemagglutinin-esterase and spike proteins PROTEIN co-evolve for functional balance and optimal virion avidity

    Authors: Yifei Lang; Wentao Li; Zeshi Li; Danielle Koerhuis; Arthur C.S. van den Burg; Erik Rozemuller; Berend-Jan Bosch; Frank J.M. van Kuppeveld; Geert-Jan P.H. Boons; Eric G. Huizinga; Hilde M. van der Schaar; Raoul J. de Groot

    doi:10.1101/2020.04.03.003699 Date: 2020-04-05 Source: bioRxiv

    Human coronaviruses OC43 and HKU1 are respiratory pathogen of zoonotic origin that have gained worldwide distribution. OC43 apparently emerged from a bovine coronavirus (BCoV) spill-over. All three viruses attach to 9-O-acetylated sialoglycans via spike protein S PROTEIN with hemagglutinin-esterase HE acting as a receptor-destroying enzyme. In BCoV, an HE lectin domain promotes esterase activity towards clustered substrates. OC43 and HKU1, however, lost HE lectin function as an adaptation to humans. Replaying OC43 evolution, we knocked-out BCoV HE lectin function and performed forced evolution-population dynamics analysis. Loss of HE receptor-binding selected for second-site mutations in S, decreasing S binding affinity by orders of magnitude. Irreversible HE mutations selected for cooperativity in virus swarms with low-affinity S minority variants sustaining propagation of high-affinity majority phenotypes. Salvageable HE mutations induced successive second-site substitutions in both S and HE. Apparently, S and HE are functionally interdependent and co-evolve to optimize the balance between attachment and release. This mechanism of glycan-based receptor usage, entailing a concerted, fine-tuned activity of two envelope protein PROTEIN species, is unique among CoVs, but reminiscent of that of influenza A viruses (IAVs). Apparently, general principles fundamental to virion-sialoglycan interactions prompted convergent evolution of two important groups of human and animal pathogens.

    Epitope-based chimeric peptide vaccine design against S, M and E proteins PROTEIN of SARS-CoV-2 etiologic agent of global pandemic COVID-19 MESHD: an in silico approach

    Authors: M. Shaminur Rahman; M. Nazmul Hoque; M. Rafiul Islam; Salma Akter; A. S. M. Rubayet-Ul-Alam; Mohammad Anwar Siddique; Otun Saha; Md. Mizanur Rahaman; Munawar Sultana; M. Anwar Hossain

    doi:10.1101/2020.03.30.015164 Date: 2020-03-31 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing pandemic of coronavirus disease 2019 MESHD ( COVID-19 MESHD), a public health emergency of international concern declared by the World Health Organization (WHO). An immuno-informatics approach along with comparative genomic was applied to design a multi-epitope-based peptide vaccine against SARS-CoV-2 combining the antigenic epitopes of the S, M and E proteins PROTEIN. The tertiary structure was predicted, refined and validated using advanced bioinformatics tools. The candidate vaccine showed an average of [≥] 90.0% world population coverage for different ethnic groups. Molecular docking of the chimeric vaccine peptide with the immune receptors ( TLR3 HGNC and TLR4 HGNC) predicted efficient binding. Immune simulation predicted significant primary immune response with increased IgM and secondary immune response with high levels of both IgG1 and IgG2. It also increased the proliferation of T-helper cells and cytotoxic T-cells along with the increased INF-{gamma} and IL-2 HGNC cytokines. The codon optimization and mRNA secondary structure prediction revealed the chimera is suitable for high-level expression and cloning. Overall, the constructed recombinant chimeric vaccine candidate demonstrated significant potential and can be considered for clinical validation to fight against this global threat, COVID-19 MESHD.

    Presence of SARS-Coronavirus-2 in sewage

    Authors: Gertjan Medema; Leo Heijnen; Goffe Elsinga; Ronald Italiaander; Anke Brouwer

    doi:10.1101/2020.03.29.20045880 Date: 2020-03-30 Source: medRxiv

    In the current COVID-19 MESHD COVID-19 MESHD pandemic, a significant proportion of cases shed SARS-Coronavirus-2 (SARS-CoV-2) with their faeces. To determine if SARS-CoV-2 is present in sewage during the emergence of COVID-19 MESHD in the Netherlands, sewage samples of 7 cities and the airport were tested using RT-PCR against three fragments of the nucleocapsid protein PROTEIN gene (N1-3) and one fragment of the envelope protein PROTEIN gene (E PROTEIN). No SARS-CoV-2 was detected in samples of February 6, three weeks before the first case was reported in the Netherlands on February 27. On March 5, the N1 fragment was detected in sewage of five sites. On March 15/16, the N1 fragment was detected in sewage of six sites, and the N3 and E fragment were detected at 5 and 4 sites respectively. This is the first report of detection of SARS-CoV-2 in sewage. The detection of the virus in sewage, even when the COVID-19 MESHD incidence is low, indicates that sewage surveillance could be a sensitive tool to monitor the circulation of the virus in the population.

    Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies

    Authors: Daniel Wrapp; Dorien De Vlieger; Kizzmekia S Corbett; Gretel M Torres; Wander Van Breedam; Kenny Roose; Loes van Schie; - VIB-CMB COVID-19 Response Team; Markus Hoffmann; Stefan Pöhlmann; Barney S Graham; Nico Callewaert; Bert Schepens; Xavier Saelens; Jason S McLellan

    doi:10.1101/2020.03.26.010165 Date: 2020-03-28 Source: bioRxiv

    The pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) MESHD, severe acute respiratory syndrome coronavirus (SARS-CoV-1) MESHD and COVID-19 MESHD coronavirus (SARS-CoV-2) have all emerged into the human population with devastating consequences. These viruses make use of a large envelope protein PROTEIN called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins PROTEIN play, they represent a vulnerable target for the development of therapeutics to combat these highly pathogenic coronaviruses. Here, we describe the isolation and characterization of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs are capable of potently neutralizing MERS-CoV MESHD or SARS-CoV-1 S pseudotyped viruses. The crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs block MESHD receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S MESHD, and demonstrate that this cross-reactive VHH is capable of neutralizing SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.

    Personalized workflow to identify optimal T-cell epitopes for peptide-based vaccines against COVID-19 MESHD

    Authors: Rui Qiao; Ngoc Hieu Tran; Baozhen Shan; Ali Ghodsi; Ming Li

    id:2003.10650v1 Date: 2020-03-24 Source: arXiv

    Traditional vaccines against viruses are designed to target their surface proteins, i.e PROTEIN., antigens, which can trigger the immune system to produce specific antibodies to capture and neutralize the viruses. However, viruses often evolve quickly, and their antigens are prone to mutations to avoid recognition by the antibodies (antigenic drift). This limitation of the antibody-mediated immunity could be addressed by the T-cell mediated immunity, which is able to recognize conserved viral HLA peptides presented on virus-infected cells. Thus, by targeting conserved regions on the genome of a virus, T-cell epitope-based vaccines are less subjected to mutations and may work effectively on different strains of the virus. Here we propose a personalized workflow to identify an optimal set of T-cell epitopes based on the HLA alleles and the immunopeptidome of an individual person. Specifically, our workflow trains a machine learning model on the immunopeptidome and then predicts HLA peptides from conserved regions of a virus that are most likely to trigger responses from the person T cells. We applied the workflow to identify T-cell epitopes for the SARS-COV-2 virus, which has caused the recent COVID-19 MESHD COVID-19 MESHD pandemic in more than 100 countries across the globe.

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MeSH Disease
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SARS-CoV-2 Proteins


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