The Rise and Fall of a Local SARS-CoV-2 Variant with the Spike Protein Mutation L452R.

Orna Mor,Dana Bar-Ilan,Ital Nemet,Neta S Zuckerman,Yaniv Lustig,Shay Fleishon,Limor Kliker,Michal Mandelboim,Efrat Bucris,Ella S Mendelson,Michal Linial

doi:10.3390/vaccines9080937

Abstract

Emerging SARS-CoV-2 variants may threaten global vaccination efforts and the awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged from a local B.1.362 lineage, B.1.362+L452R. The L452R mutation is associated with the Delta and Epsilon variants and was shown to cause increased infection and reduction in neutralization in pseudoviruses. Indeed, the B.1.362+L452R variant demonstrated a X4-fold reduction in neutralization capacity of sera from BNT162b2-vaccinated individuals compared to a wild-type strain. The variant infected 270 individuals in Israel between December 2020 and March 2021, until diminishing due to the gain in dominance of the Alpha variant in February 2021. This study demonstrates an independent, local emergence of a variant carrying a critical mutation, L452R, which may have the potential of becoming a variant of concern and emphasizes the importance of routine surveillance and detection of novel variants among efforts undertaken to prevent further disease spread.

Highlights

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for substantial morbidity and mortality and has been rapidly spreading worldwide sinceDecember 2019
We describe a novel emerging variant carrying the L452R mutation that emerged from a local B.1.362 lineage, which was widespread in Israel prior to the entrance of the Alpha variant in December 2020
The novel B.1.362+L452R variant forms a distinct cluster in a phylogenetic tree representing randomly chosen sequenced samples from Israel (Figure 1A), constructed as part of the national program for SARS-CoV-2 whole genome sequencing and variant surveillance

Summary

Introduction

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for substantial morbidity and mortality and has been rapidly spreading worldwide sinceDecember 2019. Applied Pfizer and other vaccination programs have effectively reduced the prevalence of severe disease cases and the number of hospitalizations [1,2]. Variants of concern (VOC), such as B.1.1.7 (Alpha) [3], B.1.351 (Beta) [4], P.1. (Gamma) [5] and, the most recent, B.1.617.2 (Delta) [6], have emerged in the last months. The Delta variant, first emerging in India, has been already identified in ~100 countries worldwide. As VOC were shown to reduce vaccine efficacy in convalescent or vaccinated individuals [7,8,9], they may threaten global vaccination efforts and awaited reduction in outbreak burden. It is of outmost importance to monitor such VOC and identify emerging local variants via routine sequencing from random sampling of the population

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Results

Conclusion