Yu Xiaobo/Li Yongzhe team used SARS-CoV-2 full proteomic chip to fully reveal the expression and distribution of viral antibodies in serum in patients with early neo-coronapneumonia.

The novel coronavirus SARS-CoV-2 has spread to over 200 countries or regions in the world as of April 28th. Commissioning editor has reported more than 3 million confirmed cases abroad, and more than 200 thousand deaths have been reported., novel coronavirus pneumonia carriers and early new crown pneumonia patients, whose symptoms are light and hidden, are unable to be detected in a timely and effective manner, which poses enormous challenges to the epidemic prevention and control in the world. The new coronavirus encodes more than 20 kinds of proteins, which can be recognized by the human immune system and produce a large number of antibodies. Novel coronavirus pneumonia early detection of novel coronavirus pneumonia patients' serum antibody levels and changes in the level of proteome, and how to identify the antibody biomarkers in early detection of new crown pneumonia, and then develop a rapid diagnostic reagent forin future, is of great value for the timely detection and treatment of new crown disease virus infection.on March 28, 2020, researcher Yu Xiaobo of National Center for Protein Science Beijing (Phoenix Center) and Professor Li Yongzhe of Peking Union Medical College Hospital published the article sars-cov-2 protein microarray for mapping covid-19 anti body interactions at amino acid on the preprint platform biorxiv Resolution [1] (the sars-cov-2 proteome chip developed by Yu Xiaobo / Li Yongzhe cooperative team can realize panoramic scanning of serum antibody at amino acid level), and designed and developed the whole proteome peptide chip of sars-cov-2 virus.the chip contains 966 polypeptides and purified n, s and E protein probes. It takes only 1.5 hours to scan the antibody binding to the amino acid sequence of sars-cov-2 virus protein in serum and plasma of patients with new coronary heart disease.the chip can be widely used for large-scale detection of antibodies against new coronavirus, dynamic monitoring of immune response, epitope analysis of antibody reagents and drugs, and detection of diagnostic markers and therapeutic antibodies. The novel coronavirus pneumonia was released on April 20th in2020 in April 20th. The Proteome-wide analysis of differentially-expressed SARS-CoV-2 antibodies in in [2] was used to detect and analyze the expression and distribution of new crown virus antibodies in the serum of patients with early new coronavirus pneumonia and suspected patients (Fig. 1). The novel coronavirus pneumonia was used to analyze the serum antibody flow pattern of patients with early stage of new crown pneumonia. Thediagram 1. SARS-CoV-2 full proteomics chip was used to analyze the schematic map of serum antibody in patients with early stage of new crown pneumonia. Novel coronavirus pneumonia, novel coronavirus pneumonia,first, they used SARS-CoV-2 whole protein microarray to screen 40 cases of early mild new crown pneumonia, influenza and non influenza suspected patients' serum, and analyzed and identified antibodies specifically expressing IgM and IgG virus specifically for early new crown pneumonia (Fig. 2).Figure 2. Detection of differentially expressed antibodies between early new crown and suspected patients with sars-cov-2 proteomic chip. The novel coronavirus pneumonia patients were identified by(a) and (b). The results showed that: 1) the specific IgM antibodies against new crown pneumonia were mainly S protein. However, IgG antibody can be N protein, S protein and orf1ab protein; 2) patients with newly diagnosed new coronavirus have a great bias towards different antigens of new coronavirus.among them, the immunogenicity of N antigen is very strong and the sensitivity of detection is low. The novel coronavirus pneumonia isand S antigen is more specific and sensitive for early detection of new crown pneumonia, but it has bias towards IgM and IgG antibodies.among them, the best markers of IgM antibody are S1 + s2ecd or s1-rbd protein, and the best antibody markers of IgG antibody can be s2ecd and S1 + s2ecd protein (Fig. 3). Novel coronavirus pneumonia N and S protein levels were detected in serum ofpatients with suspected new crown pneumonia and clinically suspected patients in the serum of 3..(a) and (b) were the differential expression of human IgM and IgG antibodies with N and S protein respectively. By further structural analysis, it was found that the antibody epitopes of s2ecd of IgM were mainly distributed on the outer surface of the protein, while the two antibody epitopes of S protein of IgG were distributed on the surface and inside of the protein respectively.while the IgG epitopes of N protein were distributed on the surface in strips, which formed the binding sites of antibodies (Fig. 4).Figure 4. The distribution of antibody epitopes of N protein and S protein was analyzed by structure analysis.(a) and (b) are the positions of IgM and IgG NCV epitopes on N and S protein structure, respectively.yellow is the antibody epitope, and the red arrow indicates the position of the antibody epitope on the protein structure. Novel coronavirus pneumonia and suspected patients withandprotein (SARS-CoV-2) and SARS-CoV-2 (2) can be distinguished from 87% and 73% by detecting IgM and IgG antibody markers, which is much higher than the existing antibody detection reagent (7%-53%). The novel coronavirus pneumonia markers identified bycan be used to develop rapid serological reagents, and then to screen new asymptomatic carriers and early new crown pneumonia patients. The results showed that the SARS-CoV-2 markers were not only sensitive to the infection of the new crown virus.Figure 5. Comparison of the positive rates of the markers identified by sars-cov-2 proteomics chip and antibody detection reagents from different manufacturers.microarray: protein chip; chemoluminescence: chemiluminescence method; ELISA: enzyme-linked immunosorbent assay; immuno colloidal gold strip: colloidal gold strip method.#1 - #7 are different manufacturers.finally novel coronavirus pneumonia antibody biomarkers and clinical data were analyzed.showed novel coronavirus pneumonia antibody marker expression was significantly correlated with clinical indicators of viral infection., novel coronavirus pneumonia antibody markers were also closely related to clinical indicators of myocardial injury (NT-proBNP and CKMB-mass) (Fig. 6). The results of novel coronavirus pneumonianot only provide a direction for developing high sensitivity serological reagents for early detection of new crown pneumonia, but also have important reference value for understanding the function of new coronavirus antibody and for clinical treatment. Novel coronavirus pneumonia patients with6.. Specific viral antibodies and clinical indicators were analyzed. The novel coronavirus pneumonia patients were(a) and (b), respectively, and the correlation between specific IgM and IgG virus antibodies and clinical indicators were analyzed. (c) and (d) specific IgM and IgG virus specific antibodies were significantly correlated with acute myocardial injury indexes (NT proBNP and CKMB mass). link: 1.references 1.hongye Wang, Xin Hou, Xiang Wu, te Liang, Xiaomei Zhang, Dan Wang, Fei Ting, Jiayu Dai, Hu Duan, Shubin Guo, Yongzhi Li, Xiaobo Yu Yu, sars-cov-2 protein microarray for mapping coved-19 anti body interactions at amino acid resolution.biorxiv 2020.03.26.99474756; doi: xiaomei2020.03.26.99474756; doi: Xiao: xiaomei2020.03.26.99474756; doi: Xiao: xiaomeivo2020.03.26.99474756; doi: Xiao: Xiao: xiaomeidoi: 2020.03.26.9947i Zhang, Xian Wu, Dan Wang, Minya Lu, Xin Hou, Hongye Wang, Te Liang, Jiayu Dai, Hu Duan, Yingchun Xu, Yongzhe Li, Xiaobo Yu. Proteome-wide analysis of differentially-expressed SARS-CoV-2 antibodies in early COVID-19 infection. medRxiv 2020.04.14.20064535; doi: