Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) plays critical roles in host cell entry. Non-synonymous substitutions affecting S are not uncommon and have become fixed in a number of SARS-CoV-2 lineages. A subset of such mutations enable escape from neutralizing antibodies or are thought to enhance transmission through mechanisms such as increased affinity for the cell entry receptor, angiotensin-converting enzyme 2 (ACE2). Independent genomic surveillance programs based in New Mexico and Louisiana contemporaneously detected the rapid rise of numerous clade 20G (lineage B.1.2) infections carrying a Q677P substitution in S. The variant was first detected in the US on October 23, yet between 01 Dec 2020 and 19 Jan 2021 it rose to represent 27.8% and 11.3% of all SARS-CoV-2 genomes sequenced from Louisiana and New Mexico, respectively. Q677P cases have been detected predominantly in the south central and southwest United States; as of 03 Feb 2021, GISAID data show 499 viral sequences of this variant from the USA. Phylogenetic analyses revealed the independent evolution and spread of at least six distinct Q677H sub-lineages, with first collection dates ranging from mid-August to late November 2020. Four 677H clades from clade 20G (B.1.2), 20A (B.1.234), and 20B (B.1.1.220, and B.1.1.222) each contain roughly 100 or fewer sequenced cases, while a distinct pair of clade 20G clusters are represented by 754 and 298 cases, respectively. Although sampling bias and founder effects may have contributed to the rise of S:677 polymorphic variants, the proximity of this position to the polybasic cleavage site at the S1/S2 boundary are consistent with its potential functional relevance during cell entry, suggesting parallel evolution of a trait that may confer an advantage in spread or transmission. Taken together, our findings demonstrate simultaneous convergent evolution, thus providing an impetus to further evaluate S:677 polymorphisms for effects on proteolytic processing, cell tropism, and transmissibility.

Increased transmission of SARS-CoV-2 lineage B.1.1.7 (VOC 2020212/01) is not accounted for by a replicative advantage in primary airway cells or antibody escape

“…These variants share many convergent or parallel mutations of S as well as in NSP6 and ORF8 suggesting that these mutations are likely adaptive and likely multiple mutations are needed for an increase in transmissibility. It is notable that several emerging variants contain mutations which could increase cleavage of S. These include other mutations adjacent to the cleavage site such as P681R, Q677H, and Q677P (Hodcroft et al, 2021) as well as further mutations (H655Y, A701V) which are more distant in primary sequence but proximal to the furin cleavage site in the 3D structure of S.…”

B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies

“…The recent emergence of SARS-CoV-2 variants raises concerns both with regard to vaccine efficacy and the effectiveness of monoclonal antibody therapy. The vast majority of sequenced SARS-CoV-2 isolates contain a D614G mutation in the spike protein [3] that increases viral infectivity and transmissibility [4][5][6] and subsequently, variants with multiple mutations in the spike protein and enhanced transmissibility have emerged in the United Kingdom [7][8][9], South Africa [10], Brazil [11] and the United States [12,13] raising concerns of diminished neutralization by immune sera-elicited antibodies and escape from therapeutic monoclonal antibodies.…”

A recombinant ‘ACE2 Triple Decoy’ that traps and neutralizes SARS-CoV-2 shows enhanced affinity for highly transmissible SARS-CoV-2 variants

“…SARS-CoV-2 variants have rapidly swept the globe [1][2][3] and very recent investigations reveal that several of these variants have shown the ability to escape neutralization by convalescent antibodies in recovered COVID-19 patients 4 and recombinant neutralizing antibodies (nAbs) developed as therapeutics. 5,6 There are also fears that current vaccines may not be as effective against some of the variants and early evidence suggests that for some vaccines, this risk may exist.…”