Novel neutralizing chicken IgY antibodies targeting 17 potent conserved peptides identified by SARS-CoV-2 proteome microarray, and future prospects
Jin Li, Te Liang, Ailian Hei, Xiangbin Wang, Huijun Li, Xiaobo Yu, Rui Zhao, Peng Gao, Cong Fang, Ji Zhou, Maogang Li, Ellen He, Sven Skog
Abstract
Introduction An approach toward novel neutralizing IgY polyclonal antibodies (N-IgY-pAb) against SARS-CoV-2 S-ECD was developed. Material and methods The novel N-IgY-pAb and its intranasal spray response against the wild type (“‘WH-Human 1”) SARS-CoV-2 virus, variants of Delta or Omicron were up to 98%. Unique virus peptides binding to N-IgY-pAb were screened by a SARS-CoV-2 proteome microarray. Results 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 ( 461 LKPFERDISTEIYQA 475 ), two are in the NTD domain ( 21 RTQLPPAYTNSFTRG 35 , 291 CALDPLSETKCTLKS 305 ) four are in the C1/2-terminal ( 561 PFQQFGRDIADTTDA 575 , 571 DTTDAVRDPQTLEIL 585 , 581 TLEILDITPCSFGGV 595 , 661 ECDIPIGAGICASYQ 675 ), three are in the S1/S2 border ( 741 YICGDSTECSNLLLQ 755 , 811 KPSKRSFIEDLLFNK 825 , 821 LLFNKVTLADAGFIK 835 ) one target is in HR2 ( 1161 SPDVDLGDISGINAS 1175 ) and one is in HR2-TM ( 1201 QELGKYEQYIKWPWY 1215 ). Moreover, five potential peptides were in the NSP domain: nsp3-55 ( 1361 SNEKQEILGTVSWNL 1375 ), nsp14-50 ( 614 HHANEYRLYLDAYNM 642 , ORF10-3 ( 21 MNSRNYIAQVDVVNFNLT 38 , ORF7a-1( 1 MKIILFLALITLATC 15 ) and ORF7a-12 ( 1116 TLCFTLKRKTE 121 ). Discussion and conclusion We concluded that the N-IgY-pAb could effectively neutralize the SARS-CoV-2. The new findings of seventeen potent conserved peptides are extremely important for developing new vaccines and “cocktails” of neutralizing Abs for efficient treatments for patients infected with SARS-CoV-2.