Abstract

SummaryThe race to produce vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began when the first sequence was published, and this forms the basis for vaccines currently deployed globally. Independent lineages of SARS-CoV-2 have recently been reported: UK, B.1.1.7; South Africa, B.1.351; and Brazil, P.1. These variants have multiple changes in the immunodominant spike protein that facilitates viral cell entry via the angiotensin-converting enzyme-2 (ACE2) receptor. Mutations in the receptor recognition site on the spike are of great concern for their potential for immune escape. Here, we describe a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor-binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K, although K417N and N501Y act together against some important antibody classes. In a number of cases, it would appear that convalescent and some vaccine serum offers limited protection against this variant.

Highlights

  • Reports of a severe acute respiratory syndrome (SARS) emerged in December 2019, with rapidly increasing cases and deaths inWuhan, China

  • Mutational changes in B.1.351 A number of isolates of B.1.351 have been described, all of which have the key mutations K417N, E484K, and N501Y in the receptor-binding domain (RBD)

  • Coronavirus genome sequences were analyzed in both the UK, acquired from the COVID-19 Genomics UK (COG-UK) database (Tatusov et al, 2000), and South Africa, acquired from the Global Initiative on Sharing Avian Influenza Data (GISAID). It appears that B.1.1.7 and B.1.351 quickly became overwhelmingly dominant in the UK and South Africa, respectively

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Summary

Introduction

Reports of a severe acute respiratory syndrome (SARS) emerged in December 2019, with rapidly increasing cases and deaths in. The virus, SARS-coronavirus 2 (CoV-2) was rapidly identified, with the sequence published in January 2020 (Lu et al, 2020), and the disease it caused subsequently named coronavirus disease 2019 (COVID-19). 2348 Cell 189, 2348–2361, April 29, 2021 a 2021 The Author(s). Article ll estimated to have infected at least 118 million people, with 2.6 million deaths worldwide (https://www.worldometers.info/ coronavirus)

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