Meta-Analysis and Structural Dynamics of the Emergence of Genetic Variants of SARS-CoV-2.

Nicolas Castonguay,Wandong Zhang,Marc-André Langlois

doi:10.3389/fmicb.2021.676314

Abstract

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late December 2019 in Wuhan, China, and is the causative agent for the worldwide COVID-19 pandemic. SARS-CoV-2 is a positive-sense single-stranded RNA virus belonging to the betacoronavirus genus. Due to the error-prone nature of the viral RNA-dependent polymerase complex, coronaviruses are known to acquire new mutations at each cycle of genome replication. This constitutes one of the main factors driving the evolution of its relatively large genome and the emergence of new genetic variants. In the past few months, the identification of new B.1.1.7 (United Kingdom), B.1.351 (South Africa), and P.1 (Brazil) variants of concern (VOC) has highlighted the importance of tracking the emergence of mutations in the SARS-CoV-2 genome that impact transmissibility, virulence, and immune and neutralizing antibody escape. Here we analyzed the appearance and prevalence trajectory over time of mutations that appeared in all SARS-CoV-2 genes from December 2019 to April 2021. The goal of the study was to identify which genetic modifications are the most frequent and study the dynamics of their propagation, their incorporation into the consensus sequence, and their impact on virus biology. We also analyzed the structural properties of the spike glycoprotein of the B.1.1.7, B.1.351, and P.1 variants for its binding to the host receptor ACE2. This study offers an integrative view of the emergence, disappearance, and consensus sequence integration of successful mutations that constitute new SARS-CoV-2 variants and their impact on neutralizing antibody therapeutics and vaccines.

Highlights

In late December 2019, a new betacoronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-COV2) emerged in the city of Wuhan in the province of Hubei, China (Zhu et al, 2020)
We present a retrospective metadata analysis of mutations throughout the SARS-CoV-2 genome that reached at least a 1% worldwide frequency between December 2019 and January 2021. We investigated their frequency trajectory over time and their fixation into the reference sequencing using the Global Initiative on Sharing Avian Influenza Data (GISAID) (Shu and McCauley, 2017)
Similar to the United Kingdom and South African variants, we present in Figure 8C mutations in the S protein that are characteristic of the P.1 variant and their frequencies from December 2019 to April 30, 2021

Summary

Introduction

In late December 2019, a new betacoronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-COV2) emerged in the city of Wuhan in the province of Hubei, China (Zhu et al, 2020). Mutations occur when viral replication enzymes introduce errors in the viral genome resulting in the creation of premature termination codons, deletions, and insertions of nucleotides that can alter open reading frames and result in amino acid substitutions in viral proteins. These mutations, combined with the selective pressure of the human immune system, lead to the selection and evolution of viral genomes (Drake, 1993; Peck and Lauring, 2018). SARS-CoV-2 and other coronaviruses have low known occurrences of recombination between family members (i.e., genetic shift), and are mostly susceptible to genetic drift (Rausch et al, 2020)

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