Emergence in southern France of a new SARS-CoV-2 variant harbouring both N501Y and E484K substitutions in the spike protein

Abstract

SARS-CoV-2 variants have become a major virological, epidemiological, and clinical concern, particularly with regard to the risk of escape from vaccine-induced immunity. Here, we describe the emergence of a new variant, with the index case returning from travel in Cameroon. For 13 SARS-CoV-2-positive patients living in the same geographical area of southeastern France, a qPCR test for screening variant-associated mutations showed an atypical combination. The genome sequences were obtained by next-generation sequencing with Oxford Nanopore Technologies on GridION instruments within about 8 h. Analysis revealed 46 nucleotide substitutions and 37 deletions, resulting in 30 amino acid substitutions and 12 deletions. Fourteen of the amino acid substitutions, including N501Y and E484K, and nine deletions are located in the spike protein. This genotype pattern led to the establishment of a new Pangolin lineage, named B.1.640.2, that is a phylogenetic sister group to the old B.1.640 lineage, which has now been renamed B.1.640.1. The lineages differ by 25 nucleotide substitutions and 33 deletions. The combination of mutations in these isolates and their phylogenetic position indicate, based on our previous definition, that they represent a new variant, which we have named “IHU”. These data are a further example of the unpredictability of the emergence of SARS-CoV-2 variants, and of their possible introduction into a given geographical area from abroad.

Antigenicity comparison of SARS‐CoV‐2 Omicron sublineages with other variants contained multiple mutations in RBD

“…The B.1.630 variant, first discovered in the Dominican Republic, contains 12 mutations in the spike protein, of which the RBD contains three mutations, L452R, T478R, and E484Q 15 . In December 2021, the B.1.640 variants were found in many countries, and the sequences of its derivatives B.1.640.1 and B.1.640.2 are highly consistent 17 . The B.1.640.1 variant contains 22 mutations in spike protein, of which the RBD contains five mutations of R346S, N394S, Y449N, F490R, and N501Y.…”

“…15 In December 2021, the B.1.640 variants were found in many countries, and the sequences of its derivatives B.1.640.1 and B.1.640.2 are highly consistent. 17…”

Whole-body metabolic modelling predicts isoleucine dependency of SARS-CoV-2 replication

“…Interestingly, the predicted virus replication rates varied significantly between the variants (Figure 4B). The delta variant achieved the highest shedding rate followed by B.1.640, a variant under monitoring by the WHO, which had been reported in France in December 2021 [57], and its occurrence overlapped with the omicron wave. The maximal virus shedding rate predicted for the omicron variant, which now represents the dominant variant worldwide, was lower than that of the parental strain (Figure 4B, Table S8).…”

Efficient antibody evasion but reduced ACE2 binding by the emerging SARS-CoV-2 variant B.1.640.2

“…The most prominent example is the highly mutated Omicron variant, which infects convalescent or vaccinated individuals with unprecedented efficiency [ 1 , 2 ], highlighting the threat that emerging SARS-CoV-2 variants pose to efforts to control the pandemic. Recently, a novel SARS-CoV-2 variant, B.1.640.2, which harbors an unusually high number of mutations in the S protein, was detected in southern France [ 3 ]. Here, we analyzed the impact of these mutations on viral cell tropism, ACE2 interactions, and antibody-mediated neutralization.…”

“…The B.1.640.2 variant was detected in November 2021 in a vaccinated adult patient who had returned from Cameroon and exhibited mild respiratory symptoms [ 3 ]. B.1.640.2 infection was also detected in 12 other individuals living in the same area [ 3 ]. The B.1.640.2 S protein analyzed in the present study harbors 13 amino acid substitutions and two deletions (Fig.…”