AUTHOR=Li Jin , Liang Te , Hei Ailian , Wang Xiangbin , Li Huijun , Yu Xiaobo , Zhao Rui , Gao Peng , Fang Cong , Zhou Ji , Li Maogang , He Ellen , Skog Sven TITLE=Novel neutralizing chicken IgY antibodies targeting 17 potent conserved peptides identified by SARS-CoV-2 proteome microarray, and future prospects JOURNAL=Frontiers in Immunology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1074077 DOI=10.3389/fimmu.2022.1074077 ISSN=1664-3224 ABSTRACT=An approach toward novel neutralizing IgY polyclonal antibodies (N-IgY-pAb) against SARS-Cov-2 S-ECD was developed. The novel N-IgY-pAb and its intranasal spray response against the wild type (“'WH-Human 1”) SARS-Cov-2 virus, variants of Delta and Omicron was up to 98%. Unique virus peptides binding to N-IgY-pAb were screened by a SARS-Cov-2 proteome microarray. Seventeen mutation-free peptides with a Z-score > 3.0 were identified as potent targets from a total of 966 peptides. The new findings show that one is in the RBM domain (461LKPFERDISTEIYQA475), two are in the NTD domain (21RTQLPPAYTNSFTRG35, 291CALDPLSETKCTLKS305), four are in the C1/2-terminal (561PFQQFGRDIADTTDA575, 571DTTDAVRDPQTLEIL585, 581TLEILDITPCSFGGV595, 661ECDIPIGAGICASYQ675), three are in the S1/S2 border (741YICGDSTECSNLLLQ755, 811KPSKRSFIEDLLFNK825, 821LLFNKVTLADAGFIK835), one target is in HR2 (1161SPDVDLGDISGINAS1175) and one is in HR2-TM (1201QELGKYEQYIKWPWY1215). Moreover, five potential peptides were in the NSP domain: nsp3-55 (1361SNEKQEILGTVSWNL1375), nsp14-50 (6144HHANEYRLYLDAYNM6425), ORF10-3 (21MNSRNYIAQVDVVNFNLT38), ORF7a-1 (1MKIILFLALITLATC15) and ORF7a-12 (111TLCFTLKRKTE121). We concluded that the N-IgY-pAb effectively neutralizing the SARS-CoV-2. The new findings of seventeen potent conserved peptides are extremely important for development of new vaccines and “cocktails” of neutralizing Abs for efficient treatment of patients infected with SARS-CoV-2.