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 ((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.