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

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

Front Microbiol. 2021 Jun 29:12:676314. doi: 10.3389/fmicb.2021.676314. eCollection 2021.

Authors

Nicolas Castonguay¹, Wandong Zhang^{2

3}, Marc-André Langlois^{1

4}

Affiliations

¹ Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
² Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
³ Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON, Canada.
⁴ uOttawa Center for Infection, Immunity and Inflammation (CI3), Ottawa, ON, Canada.

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.

Keywords: B.1.1.7 variant; B1.351 variant; COVID-19; Coronavirus; P.1 variant; SARS-CoV-2; evolution; variants.