The 249RWMD spike protein insertion in Omicron BQ.1 subvariant compensates the 24LPP and 69HV deletions and may cause severe disease than BF.7 and XBB.1 subvariants

Abstract

Abstract Alarming antibody evasion properties were documented for new BF, BQ and XBB Omicron subvariants. Most immune-drugs were inactive neutralizing those COVID-19 subvariants and viral titers were exceptionally low as compared to deadly B.1.1.7, B.1.617.2 and B.1.1.529 variants with D614G, N501Y and L452R mutations in spike. The 91% nucleotides changes in spike protein of BQ.1 were resulted in AA changes whereas only 52% nucleotides changes resulted in AAs changes in ORF1ab. The N460K and K444T mutations in BQ.1 may be important driving force for immune-escape similar to F486S and N480K mutations in BA.2.75 subvariant and related XBB.1 subvariant. Further, the R346T mutation as found in BA.4.6 and BF.7, was regained in BQ.1.1 and BA.2.75.2 to enhance immune escape and infectivity (> 80%). The L452R and F486V mutations in spike were main drivers of Omicron BA.2 conversion to BA.4 and BA.5 in presence of 69HV deletion. Whereas 24LPP spike deletion and 3675SGF ORF1ab protein deletion were found in all Omicron viruses including BQ.1 and XBB.1. Interestingly, we found about 211 COVID-19 sequences with four amino acids (249RWMD) insertion near the RBD domain of Omicron viruses similar to 215EPE three amino acids insertion in Omicron BA.1 variant. Such sequences first detected in California and extended to Florida, Washington and Michigan as well as other adjoining US states. An one amino acid deletion (140Y) in spike was also found in BA.4.6, BQ.1.5, BQ.1.8, BQ.1.14, BQ.1.1.5, XBB.1 as well as related AZ.3, BU.1, BW.1, CR.2, CP.1 and CQ.1 subvariants but was not detected in BA.2.75, BF.7, XBD, BQ.1, BQ.1.1, BQ.1.2, BQ.1.6, BQ.1.10, BQ.1.12, BQ.1.16, BQ.1.19, BQ.1.22, BQ.1.1.1, BQ.1.1.4, BQ.1.1.12 and related BK.1, BN.1, BM.1.1.1, BR.2, BU.1, CA.1, CD.2, CH.1.1 subvariants. Thus, BQ.1 insertion was compensated the other deletions and would be more infectious than BA.2.75, BF.7 and XBB.1 subvariants even there was a 26nt deletion in the 3’-UTR. The spike protein R341T one amino acid change in BQ.1.1 and BQ.1.1.1 might be important but no 249RWMD insertion.