The Unique Deletion, Insertion and Point Mutation in The Upstream of Nucleocapsid (N) Gene of Different Covid-19 Variants Suggests Differential Translational Mechanisms of N-Protein

Abstract

Asit Kumar Chakraborty

The nucleocapsid protein (N protein; 219 AAs) of SARS-CoV-2 was synthesized from terminal part of the ~30kb genome and a 31ERS three AAs deletion was reported in all Omicron variants but not in Alpha, Beta, Gamma and Delta variants. We found that upstream of N-gene which also a part of ORF8 gene has different deletion, insertion and point mutations in different corona virus lineages. As for example, 119DF two amino acids (5’-28243GATTTC-3’) deletion was found in ORF8 protein of Delta variants located adjacent to the N-gene upstream. Similarly, four nucleotides (5’-AACA-3’) insertion at 28262 position was found in the Gamma (P.1) variant only. Whereas all Omicron variants (BA.1/BA.2/BA.4/ BA.5) and subvariants (XBB.1.5, BQ.1.1) which were spreading now with mild diseases, have no such deletion or inser- tion. Some point mutations T>C at 28247 position were found in Alpha variants in that small region of N-gene upstream. Moreover, “GAT” sequence at 28279 position in Gamma variant similar to Wuhan and Beta (B.1.351), was changed to “CTA” in Alpha variant (B.1.1.7) at the N-gene upstream. The extra “A” at 28273 position in Alpha variant (also found in Wuhan and Gamma) was equally distributed (“AAA” vs “AAAA”) as judged by BLAST-N search but it was not instrumental if there was a sequence error. The differential hairpin structures were obtained with upstream of Delta and Gamma but no such difference was noticed with hairpin structures of different Omicron N-gene upstream. We suggest that hairpin structures with higher δG specifically in Gamma variant (P.1) may reduce the translation of N-protein and may be the one of the causes of extinct of that lineage of corona virus.

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