Dominant and sustained mutations, deletions, and insertions in the Omicron coronavirus lineages JN.1, KP.3, LB.1, XEC, MC.1, and MV.1

The JN.1 Omicron coronaviruses possess a unique 16MPLF spike insertion that compensates for deletions at positions 24LPP, 31S, 69HV, 145Y, 211N, and V483 in the spike protein. These viruses also exhibit a 3576SGF deletion in the open reading frame (ORF)1ab protein, 26–49 nucleotide deletions in the 3’-untranslated region (UTR), and a 31ERS amino acid deletion in the N protein. In an ongoing analysis of JN.1 lineages, an N30 deletion in the spike was detected. This N30 deletion was found in many subvariants, suggesting viral instability and low penetration. SWISS-MODEL analysis revealed that the 30N deletion mutants exhibit a more compact and symmetrical three-dimensional spike structure. The modeling was performed using templates 7nc8.1.A (88.8% similarity) and 8x4h.1.A (99.07% similarity). In the resulting models, His440 was positioned as the first amino acid to interact with the angiotensin-converting enzyme receptor (ACE). However, the JN.1-derived 8y5j.1.A template showed a flattened trimeric spike with protruding residues engaging the receptor. Moreover, a T44I mutation in the nsp2 ribonucleic acid topoisomerase (XLQ96433), a potential drug target, was identified. The T224I ORF1ab mutation occurred in ~300 subvariants. Further analysis identified several important mutations in the ORF1ab polyprotein. The mutations T19I, S50L, V127F, G339H, K356T, S371F, S373P, S375F, R403S, K417N, V455H, G446S, N460K, S477K, Q493E, and Y505H were identified in the spike protein of JN.1 lineages. Moreover, the mutations P13L, Q229K, and S413R in N protein, A63T in M protein, T223I in ORF3a, and F19L in ORF7b protein were observed within the newly studied JN.1 lineage. A 26-nucleotide deletion in the 3’-UTR was highly prevalent (99%), while a 49-nucleotide deletion was observed less frequently. In addition, mutations in the accessory proteins (A68V in XEC.2, H144Q in XEC.3, and G71R in XEC.5) were found, suggesting that recent mutations are clustered in the NH2-terminus of the spike protein.