New research examines the elimination of the B.1.362 + L452R variant in Israel

Is it possible to completely get rid of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants? New research led by Neta S. Zuckerman of Sheba Medical Center in Israel suggests it’s possible. Their report details the upsurge of a B.1.362 variant harboring the L452R mutation that eventually disappeared due to vaccination efforts and the presence of more robust variants.

Variants can easily circulate worldwide because of mutations that make it more difficult for the immune system to detect and neutralize the virus. For example, L452R is a mutation found in the Delta and Epsilon (B.1.429) variant that helps SARS-CoV-2 with immune evasion and increased infectivity. L452R on the Epsilon and Delta variant has previously shown to have a 6.7 and a 5.8-fold reduction in neutralizing activity.

This study demonstrated a X4-fold decrease in neutralization capacity of sera derived from fully vaccinated individuals against the B.1.362+L452R variant, suggesting that it is this mutation that accounts for the impact on the neutralization potential of the different variants that carry the L452R mutation,” explained the research team.

Combined with L452R, the researchers claim the virus is capable of becoming a variant of concern. While B.1.362 + L452R later disappeared from the local population, they advise more routine surveillance to detect and prevent the rise of other future variants.

The study “The rise and fall of an emerging SARS-CoV-2 variant with the spike protein mutation L452R” is available as a preprint on the medRxiv* server.

Emergence of B.1.362 + L452R

The research team randomly selected SARS-CoV-2 samples that were confirmed positive through PCR testing in Israel. Viral genomes were extracted and analyzed from samples.

A B.1.362 variant carrying the L452R mutation was detected in Israel that was a part of the B.1.362 lineage — a widespread lineage until December 2020 when Alpha (B.1.1.7) became the dominant variant.

While the B.1.362 lineage has been found in other countries, the researchers note the sequences of this lineage representing B.1.362 + L452R originally came from Israel.

Genetic make-up of novel variant

The B.1.362 + L452R has two non-synonymous mutations in the spike protein — L1063F and L452R on the receptor-binding domain (RBD). There is also a non-synonymous mutation in the NSP16 gene in D2179Y and a synonymous mutation in the membrane protein in G26840A.

A W131C mutation on the ORF3a gene was detected in the variant later on and is now present in most variant sequences.

Prevalence of variant in Israel

The variant appeared to disappear from the population over time. From 854 randomly sequenced samples in December 2020, only 6% were from the variant. Since April 2021, no random sampling of coronavirus samples belonged to B.1.362 + L452R.

Since April 2021, there have been 270 individuals living in Israel infected with the B.1.362 + L452R variant.

The noticeable decline of B.1.362 + L452R corresponds with the decline of the B.1.362 lineage overall in Alpha. B.1.362 decreased from 19% in December 2020 to 0% in April 2021.

This was likely due to the spread of the Alpha variant, which decreased the prevalence of all local lineages. Alpha later became Israel’s dominant SARS-CoV-2 variant in February 2021. The vaccination campaign held in Israel in December 2020 may have also contributed to the decline of B.1.362.

By April 2021, the researchers note the B.1.362+L452R variant is no longer observed in routine sequencing and is considered completely eliminated. However, the threat of other variants harboring L452R remains.

The identification of this locally-emerging variant carrying the L452R mutation, accompanied by additional independently-emerging variants carrying the same mutation (Delta and additional B.1.617 lineage variants, Epsilon, A.27.1), emphasizes the relevance of the L452R mutation to the virus adaptiveness,” wrote the researchers.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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