Two Short Low Complexity Regions (LCRs) are Hallmark Sequences of the Delta SARS-CoV- 2 Variant Spike Protein

Low complexity regions (LCRs) are protein sequences formed by a set of compositionally biased residues. LCRs are extremely abundant in cellular proteins and have also been reported in viruses, where they may partake in evasion of the host immune system. Here we report four novel extremely conserved LCRs in the spike proteins of several SARS-CoV-2 variants. With the exception of Iota, where it is absent, the Spike LCR-1 is present in the signal peptide of 80.57% of the Delta variant, and in other variants of concern and interest. The Spike LCR-2 is highly prevalent (79.87%) in Iota. Two distinctive LCRs are present in the Delta spike protein. The Delta Spike LCR-3 is present in 99.19% of the analyzed sequences, and the Delta Spike LCR-4 in 98.3% of the same set of proteins. These two LCRs are present in the furin cleavage site and HR1 domain, respectively, and may be considered hallmark traits of the Delta variant. The presence of two medically-important point mutations, P681R and D950N, in these LCRs, combined with the extraordinary conservation of these regions, suggests that they may be a trait associated with the rapid spread of the highly contagious Delta lineage.