The G36S, M147I, G265S, T568I, N852S new mutations in the Spike of Omicron JN.1 subvariants: New subvariants JN.1.1 to JN.1.5 nomenclature and oligonucleotides design for JN.1 subvariants detection

Abstract

The JN.1 omicron coronavirus spread is havoc. Recently, few old people were died following JN.1 infections with co-morbidity. We are tracking the new mutation profiles of JN.1, JN.2 and JN.3 coronaviruses in the database to predict the newer mutations in the spike that could be important for virus entry in the lung cells. The SARS-CoV-2 sequences deposited on 12th January, 2024 by Opentrons P and Howard D were analyzed in a pilot scale. The new spike mutations in the JN.1 variants were found as: G36S (accession no. PP115250), M147I (accession no. PP116273), T568I (accession no. PP115301) and N852S (PP106538). The role of such mutations located outside the RBD region of spike was not known but NH2-terminal deletions (24LPP, 69HV, 143VYY) and insertions (17MPLF, 147RWMD) were allowed in different omicron variants. BLASTP search with G36S-peptide produced six identical sequences deposited by four independent US investigators with spike 17MPLF insertion and L452S mutation but new T568I (OR941013) and N852S (PP106538) spike mutations were found. BLASTP search with T568I-peptide gave 25 identical sequences deposited by eight independent US investigators demonstrating T568I mutation in the spike was authentic. Multi-alignment of those spike detected T568I mutation but PP030032 sequence had no 17MPLF insertion and PP051563 sequence had no L452S mutation being pre-JN.1 lineages. Similarly, M147I-peptide produced seven 100% similarity sequences. But the sequences OR082643, OR985352 and OR833719 had no L452S mutation and PP029920 had no 17MPLF insertion being pre-JN.1 variants whereas PP077772, PP016544 and OR976328 appeared authentic JN.1 and G265S spike mutation in PP106544 was new. The new mutations detected in the ORF1ab polyprotein nsp3 protein were: E1559K and T1998A mutations (accession no. PP116246) and S2500F mutation (accession no. PP116233). Thus, characterized JN.1 RefSeq sequences with L452S mutation plus other new mutation in the spike were given JN.1.1 to JN.1.5 subvariants nomenclature and variant specific oligonucleotides were made for their detection after WGS. However, selection with JN.1-S-L452S-oligo and JN.123-S-MPLF-oligo must be done first and then other oligonucleotides will be used to select JN.1.1. to JN.1.5 subvariants. The T568I mutation spread suggested such spike interacted with ACE-2 receptor better similar to N501Y and D614G mutated spike whereas both dominant mutations were also appeared in JN.1.