Abstract
Following the worldwide emergence of the p.Asp614Gly shift in the Spike (S) gene of SARS-CoV-2, there have been few recurring pathogenic shifts occurring during 2020, as assessed by genomic sequencing. This situation has evolved in the last several months with the emergence of several distinct variants (first identified in the United Kingdom and South Africa) that manifest multiple changes in the S gene, particularly p.Asn501Tyr (N501Y), that likely have clinical impact. We report here the emergence in Columbus, Ohio in December 2020 of two novel SARS-CoV-2 clade 20G variants. One variant, that has become the predominant virus found in nasopharyngeal swabs in the December 2020-January 2021 period, harbors S p.Gln677His (Q677H), affecting a consensus QTQTN domain near the S1/S2 furin cleavage site, nucleocapsid (N) p.Asp377Tyr (D377Y) and membrane glycoprotein (M) p.Ala85Ser (A85S) mutations, with additional S mutations in subsets. The other variant present in two samples, contains S N501Y, which is a marker of the UK-B.1.1.7 (clade 20I/501Y.V1) strain, but lacks all other mutations from that virus. The Ohio variant is from a different clade and shares multiple mutations with the clade 20G viruses circulating in the area prior to December 2020. These two SARS-CoV-2 viruses, which we show are also present and evolving currently in several other parts of North America, add to the diversity of S gene shifts occurring worldwide. These and other shifts in this period of the pandemic support multiple independent acquisition of functionally significant and potentially complementing mutations affecting the S QTQTN site (Q675H or Q677H) and certain receptor binding domain mutations (e.g., E484K and N501Y).
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
We submit a new Figure 1 to include a phylogenetic tree with several hundred additional examples of the S Q677H 20G clade viruses from across the United States, including 1 example from a recent GISAID-uploaded 20G/677H virus from Ontario Canada from 12/24/20 that have acquired a S E484K mutation. A full phylogenetic tree of S Q677H sequences worldwide is provided in the supplement, providing support for a US-derived strain with only a few isolated occurrences outside of North America to date (some clearly travel-related), as of late January 2021. We submit a new Figure 3 to include an extensive phylogenetic analysis with now more than 20 N501Y-bearing viruses from 6 US states that are highly similar to the 20G Columbus viruses collected in December 2020/January 2021. A full phylogenetic tree of S N501Y-bearing strains is provided in the supplement to show the multiple likely independently-arising of both receptor binding domain and QTQTN/furin cleavage site mutations in the Spike protein. Based on this additional data, we discuss the idea of complementing functional or pathogenic mutation classes in the Spike protein, including the receptor binding domain (e.g. E484K and N501Y) and the QTQTN site (e.g. Q675H and Q677H). These sequential changes are currently arising both in the United 20G (Q677H and now E484K) and in the 20I/501Y.V1 strain (RBP N501Y first and now Q677H). The Methods are updated to include additional analytic methods for the expanded phylogenetic analyses.