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      A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2

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          Summary

          Effective countermeasures against the recent emergence and rapid expansion of the 2019 novel coronavirus (SARS-CoV-2) require the development of data and tools to understand and monitor its spread and immune responses to it. However, little information is available about the targets of immune responses to SARS-CoV-2. We used the Immune Epitope Database and Analysis Resource (IEDB) to catalog available data related to other coronaviruses. This includes SARS-CoV, which has high sequence similarity to SARS-CoV-2 and is the best-characterized coronavirus in terms of epitope responses. We identified multiple specific regions in SARS-CoV-2 that have high homology to the SARS-CoV virus. Parallel bioinformatic predictions identified a priori potential B and T cell epitopes for SARS-CoV-2. The independent identification of the same regions using two approaches reflects the high probability that these regions are promising targets for immune recognition of SARS-CoV-2. These predictions can facilitate effective vaccine design against this virus of high priority.

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          Highlights

          • Ten experimentally defined regions within SARS-CoV have high homology with SARS-CoV-2

          • Parallel bioinformatics predicted potential B and T cell epitopes for SARS-CoV-2

          • Independent approaches identified the same immunodominant regions

          • The conserved immune regions have implications for vaccine design against multiple CoVs

          Abstract

          Grifoni et al. identify potential targets for immune responses to the 2019 novel coronavirus (SARS-CoV-2) by sequence homology with closely related SARS-CoV and by a priori epitope prediction using bioinformatics approaches. This analysis provides essential information for understanding human immune responses to this virus and for evaluating diagnostic and vaccine candidates.

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          Most cited references24

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          Is Open Access

          Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

          Structure of the nCoV trimeric spike The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. Science, this issue p. 1260
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            Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China

            An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.
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              NetMHCpan-4.0: Improved Peptide-MHC Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data.

              Cytotoxic T cells are of central importance in the immune system's response to disease. They recognize defective cells by binding to peptides presented on the cell surface by MHC class I molecules. Peptide binding to MHC molecules is the single most selective step in the Ag-presentation pathway. Therefore, in the quest for T cell epitopes, the prediction of peptide binding to MHC molecules has attracted widespread attention. In the past, predictors of peptide-MHC interactions have primarily been trained on binding affinity data. Recently, an increasing number of MHC-presented peptides identified by mass spectrometry have been reported containing information about peptide-processing steps in the presentation pathway and the length distribution of naturally presented peptides. In this article, we present NetMHCpan-4.0, a method trained on binding affinity and eluted ligand data leveraging the information from both data types. Large-scale benchmarking of the method demonstrates an increase in predictive performance compared with state-of-the-art methods when it comes to identification of naturally processed ligands, cancer neoantigens, and T cell epitopes.
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                Author and article information

                Contributors
                Journal
                Cell Host Microbe
                Cell Host Microbe
                Cell Host & Microbe
                Elsevier Inc.
                1931-3128
                1934-6069
                16 March 2020
                8 April 2020
                16 March 2020
                : 27
                : 4
                : 671-680.e2
                Affiliations
                [1 ]Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
                [2 ]J. Craig Venter Institute, La Jolla, CA 92037, USA
                [3 ]Department of Pathology, University of California, San Diego, San Diego, CA 92093, USA
                [4 ]Department of Medicine, University of California, San Diego, San Diego, CA 92093, USA
                Author notes
                []Corresponding author alex@ 123456lji.org
                [5]

                Lead Contact

                Article
                S1931-3128(20)30166-9
                10.1016/j.chom.2020.03.002
                7142693
                32183941
                21e110d6-b1c7-46e9-a36e-e11c94cc1e1f
                © 2020 Elsevier Inc.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 13 February 2020
                : 26 February 2020
                : 5 March 2020
                Categories
                Article

                Microbiology & Virology
                sars-cov,covid-19,sars-cov-2,coronavirus,t cell epitope,b cell epitope,infectious disease,sequence conservation

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