Dominant and Sustained Mutations, Deletions and Insertions in the Omicron Coronavirus JN.1, KP.3, LB.1, XEC, MC.1 and MV.1 lineages

The JN.1 omicron coronaviruses had Unique 17MPLF spike insertion compensating 24LPP, 31S, 69HV, 145Y, 211N and 483V deletions in the spike. Such viruses also had 3576SGF deletion in the ORF1ab protein and 26nts or more 3’-UTR deletions as well as three amino acids (31ERS) deletion in the N-protein. Here, we found 30N deletion in the spike during our continuing analysis of JN.1 lineages like KP.2, LB.1.7, KP.3.1.1, SEC and MC.1 coronaviruses. A total thirty-one such coronaviruses were deposited in the GenBank during November, 2023 to December, 2024. The appearance of 30N deletion was found in many subvariants including JN.1.15.1, KP.2, KP.2.3, LB.1.7, XDK.3 and XDV.1.9.1. Thus, it appears that such coronavirus is very unstable and penetration is low. However, Swiss-Modelling of spike indicated a more compact symmetrical 3-D structure of 30NS deletion mutants with His440 as the first amino acid to interact with ACE-2 receptor using 7nc8.1.A (88.8% similarity) and 8x4h.1.A (99.07% similarity) templates. But using JN.1 derived 8y5j.1.A template trimeric spike 3-D structure was flattened or shorter and had protruding amino acids (Lys478, Gly479, Prp480 and Asn481 as well as Thr494 and Arg492 to encounter with receptor first. We also detected a T44I mutation in the Nsp2 RNA topoisomerase (XLQ96433) which was a target for drug development. The T224I ORF1ab mutation was found in about 300 coronavirus subvariants including JN.1 linages like MV.1 (PQ574026), MB.1.1.1 (PQ188371), and LB.1.7 (PQ386688). Further, the A211D mutation in nsp2; the P3395H, N2526S and A2710T mutations in nsp3 protease; the P3395H mutation in nsp5 protease; the R5713C mutation in nsp13 capping methyltransferase-RNA helicase were important ORF1ab changes. We suggested T19I, S50L, V127F, G339H, K356T, S371F, S373P, S375F, R403S, K417N, V455H, G446S, N460K, S477K, Q493E and Y505H dominant mutations (Wuhan position) in spike of JN.1 lineages. We also found the P13L, Q229K and S413R mutations in N-protein, the A63T mutation in M-protein, the T223I mutation in ORF3a and the F19L mutation in ORF7b protein which appeared dominant in new JN.1 linages studied. The 26nts deletion in the 3’-UTR was found prominent (99%) but few 49nt deletion could be observed (acc. nos. PQ685105, PQ685107, PQ701372 and PQ791363). The A68V mutation in the XEC.2, the H144Q mutation in the XEC.3 and the G71R mutation in the XEC.5 were found suggesting recent mutations were clustered in the NH2-terminus of spike.