Novel neutralizing chicken IgY antibodies targeting 17 potent conserved peptides identified by SARS-CoV-2 proteome microarray, and future prospects.

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 (LKPFERDISTEIYQA ), two are in the NTD domain (RTQLPPAYTNSFTRG, CALDPLSETKCTLKS) four are in the C1/2-terminal (PFQQFGRDIADTTDA,DTTDAVRDPQTLEIL,TLEILDITPCSFGGV, ECDIPIGAGICASYQ ), three are in the S1/S2 border (YICGDSTECSNLLLQ, KPSKRSFIEDLLFNK, LLFNKVTLADAGFIK) one target is in HR2 (SPDVDLGDISGINAS) and one is in HR2-TM (QELGKYEQYIKWPWY). Moreover, five potential peptides were in the NSP domain: nsp3-55 (SNEKQEILGTVSWNL), nsp14-50 (HHANEYRLYLDAYNM, ORF10-3 (MNSRNYIAQVDVVNFNLT, ORF7a-1(MKIILFLALITLATC) and ORF7a-12 (TLCFTLKRKTE).

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.