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      SARS-CoV-2 proteome microarray for global profiling of COVID-19 specific IgG and IgM responses

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          Abstract

          We still know very little about how the human immune system responds to SARS-CoV-2. Here we construct a SARS-CoV-2 proteome microarray containing 18 out of the 28 predicted proteins and apply it to the characterization of the IgG and IgM antibodies responses in the sera from 29 convalescent patients. We find that all these patients had IgG and IgM antibodies that specifically bind SARS-CoV-2 proteins, particularly the N protein and S1 protein. Besides these proteins, significant antibody responses to ORF9b and NSP5 are also identified. We show that the S1 specific IgG signal positively correlates with age and the level of lactate dehydrogenase (LDH) and negatively correlates with lymphocyte percentage. Overall, this study presents a systemic view of the SARS-CoV-2 specific IgG and IgM responses and provides insights to aid the development of effective diagnostic, therapeutic and vaccination strategies.

          Abstract

          Currently very little is known about how our immune system responds to SARS-CoV-2 infection. Here the authors generate a SARS-CoV-2 proteome microarray for profiling of IgG and IgM responses to COVID-19 in patients and find significant responses to ORF9b and NSP5, as well as the S1 and N proteins.

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          Most cited references31

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          Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

          In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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            A pneumonia outbreak associated with a new coronavirus of probable bat origin

            Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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              SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

              Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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                Author and article information

                Contributors
                d.men@wh.iov.cn
                zjet65@163.com
                taosc@sjtu.edu.cn
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                14 July 2020
                14 July 2020
                2020
                : 11
                : 3581
                Affiliations
                [1 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), , Shanghai Jiao Tong University, ; 200240 Shanghai, China
                [2 ]GRID grid.410604.7, Foshan Fourth People’s Hospital, ; 528000 Foshan, China
                [3 ]ISNI 0000000119573309, GRID grid.9227.e, State Key Laboratory of Virology, Wuhan Institute of Virology, , Chinese Academy of Sciences, ; 430071 Wuhan, China
                [4 ]ISNI 0000000119573309, GRID grid.9227.e, Key Laboratory of RNA Biology, Institute of Biophysics, , Chinese Academy of Sciences, ; 100101 Beijing, China
                [5 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, Bio-ID Center, School of Biomedical Engineering, , Shanghai Jiao Tong University, ; 200240 Shanghai, China
                Author information
                http://orcid.org/0000-0001-8700-7042
                http://orcid.org/0000-0003-1190-9570
                http://orcid.org/0000-0002-9210-1823
                Article
                17488
                10.1038/s41467-020-17488-8
                7360742
                32665645
                a492dca8-62a7-47b9-8119-c4674085d3fb
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 1 April 2020
                : 30 June 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 31900112
                Award Recipient :
                Funded by: Foshan Scientific and Technological Key Project for COVID-19 (NO:2020001000430)
                Funded by: National Key Research and Development Program of China Grant (No. 2016YFA0500600)
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                viral proteins,protein array analysis,viral infection
                Uncategorized
                viral proteins, protein array analysis, viral infection

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