Local emergence and decline of a SARS-CoV-2 variant with mutations L452R and N501Y in the spike protein

Abstract

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are replacing the initial wild-type strain, jeopardizing current efforts to contain the pandemic. Amino acid exchanges in the spike protein are of particular concern as they can render the virus more transmissible or reduce vaccine efficacy. Here, we conducted whole genome sequencing of SARS-CoV 2 positive samples from the Rhine-Neckar district in Germany during January-March 2021. We detected a total of 166 samples positive for a variant with a distinct mutational pattern in the spike gene comprising L18F, L452R, N501Y, A653V, H655Y, D796Y and G1219V with a later gain of A222V. This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains. These observations strongly argue for continuous and comprehensive monitoring of SARS CoV 2 evolution on a population level.

Neutralizing antibody activity against the B.1.617.2 (delta) variant 8 months after two-dose vaccination with BNT162b2 in health care workers

“…Neutralization titers were determined in titration experiments on VeroE6 cells as described previously by us [ 13 , 16 ]. SARS-CoV-2 virus stocks were produced by either amplification of the BavPat1/2020 strain (European Virus Archive) or isolation and amplification of the B.1.617.2 (delta) variant from nasopharyngeal and oropharyngeal swabs of PCR-confirmed SARS-CoV-2-positive patients, as previously described by us and others [ 13 , 17 ]. For the B.1.617.2 (delta) variant, NGS sequencing was performed, and lineage, variant assignment, and clade classification of the SARS-CoV-2 sequence was carried out using Pangolin and Nextclade as part of the Nextstrain framework.…”

Follow-up investigation and detailed mutational characterization of the SARS-CoV-2 Omicron variant lineages (BA.1, BA.2, BA.3 and BA.1.1)

“…Spike protein with this mutation has shown ability to escape some neutralising antibodies [78]. Appeared a few times independently [30,85], including a case of intra-host evolution in a immunocompromised (HIV) patient [27].…”

“…Appeared a few times independently [30, 85], including a case of intra-host evolution in a immunocompromised (HIV) patient [27].…”

Structural and functional insights into the spike protein mutations of emerging SARS-CoV-2 variants

“…The substitution of the five-member imidazole ring of His residue with the benzene-containing aromatic Tyr residue that includes a polar group modifies the existing hydrophobic local environment to a comparatively more charged environment in this region. Therefore, this mutant has been hypothesized to play a role in regulating the efficiency of S protein fusion and host cell entry in mammals [118][119][120].…”