Distinct Patterns of Emergence of SARS-CoV-2 Spike Variants including N501Y in Clinical Samples in Columbus Ohio

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).

The emerging SARS-CoV-2 variants of concern

“…N501Y rapidly spreads as part of the B.1.1.7 and 501.V2 clades with an affinity for ACE2 receptors in humans. 9,47 This has been studied and shown to be indicative of natural selection, resulting in high transmissibility within a population. 48,49 Furthermore, a newer variant referred to as B. leading to an outbreak of the D614G mutation, 53 where the (D) stands for aspartic acid at residue 614 of the spike viral protein that converts to glycine (G).…”

The Spike Proteins of SARS-CoV-2 B.1.617 and B.1.618 Variants Identified in India Provide Partial Resistance to Vaccine-elicited and Therapeutic Monoclonal Antibodies

“…The variants contain point mutations and short deletions in the spike protein driven by selective pressure for increased affinity for its receptor, ACE2, and escape from neutralizing antibody. Major variants identified to date include B.1.1.7 [1, 2], B.1.351 [3], B.1.526 [4], P.1 [5], P.3 (EpiCoVTM database of the Global Initiative for Sharing All Influenza Data (GISAID) : accession numbers EPI_ISL_1122426 to EPI_ISL_ 1122458) and mink cluster 5 [6]. The variants have increased transmissibility, a feature that is, at least in part, the result of mutations in the spike protein that allow for increased ACE2 affinity and/or resistance to antibody.…”

SARS-CoV-2 genome surveillance in Mainz, Germany, reveals convergent origin of the N501Y spike mutation in a hospital setting

“…This lends further evidence to the hypothesis of convergent evolution of the N501Y change. In fact, a genome surveillance group based in Ohio, USA, very recently also reported such local emergence of N501Y from a still different viral clade, 20C (Tu et al 2021). This scenario suggests that the N501Y mutation is an initial key event in driving the evolutionary success of SARS-CoV-2, and its emergence should be monitored world-wide with attention.…”