Biological and Medicinal Chemistry

Geographical Distribution of Amino Acid Mutations in Human SARS-CoV-2 Orf1ab Poly-Proteins Compared to the Equivalent Reference Proteins from China



Mutations in orf1ab poly-protein sequences from human SARS-CoV-2 isolates representing six geographical locations were identified by comparing with the equivalent reference sequences from the Wuhan-Hu-1, China isolate, epicentre of the current COVID-19 pandemic disease. The orf1ab poly-proteins of sequence length 7096 amino acid residues representing 10,929 genomes from six geographical locations comprised a total of 27,895 mutations that corresponded to 2,095 distinct mutation sites. The percentage of mutations was significantly high for RdRp (33.47%), nsp2 (20.04%), helicase (15.95%) and nsp3 (12.61%) proteins, compared to rest of the proteins which ranged between (0.14%) for nsp10 to (2.79%) for nsp6 proteins. A total of 2715 mutations were observed for the unique mutation sites identified for each of the six geographical locations. The distribution of the mutations was; Africa (87), Asia (605), Europe (134), North America (1677), Oceania (200) and South America (12). The RdRp protein contained significantly high mutation percentage (>31%) that varied among the different geographical locations. The nsp2 proteins from Asia, North America, Oceania and South America, the nsp3 proteins from Africa and Europe and the helicase proteins from North America showed high mutation percentage next to the RdRp proteins. The P4715L mutation in RdRp, T265I in nsp2 and L3606F in nsp6 were observed in all the geographical locations with the RdRp P4715L mutation being predominant among the orf1ab poly-proteins. In another dataset comprising 158 genomes in which the orf1ab poly-proteins comprised sequences of variable length between 7084-7095 amino acid residues, 88 additional distinct mutations were observed for the six geographical locations that included deletion mutations. The proteins containing deletion mutations were; leader protein, nsp2, nsp3, nsp4, nsp6, RdRp, 3’ -to-5’ exonuclease and endoRNAse.

In this work, all the mutations observed in 11,087 orf1ab poly-proteins of human SARS CoV-2 comprising between 7084-7096 amino acid residues with reference to the human SARS-CoV-2 orf1ab poly-protein sequences from Wuhan-Hu-1, China and representing the six geographical locations; Africa, Asia, Europe, North America, Oceania and South America are presented.

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Supplementary material

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