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. Graphical Abstract Errors are regularly made when SARS-CoV-2 replicates its RNA genome. The viral polymerase complex is error-prone with imperfect proofreading abilities. These errors or mutations often lead to deleterious or neutral effects on the virus. However, sometimes these mutations have a positive effect and create genetic variants of the virus with different features including increased transmissibility, pathogenicity, and immune escape capabilities. When mutations work collaboratively to create a new virus feature, this is called epistasis.
【저자키워드】 COVID-19, Evolution, SARS-CoV-2, coronavirus, variants, B.1.1.7 variant, P.1 variant, B1.351 variant, 【초록키워드】 neutralizing antibody, Brazil, ACE2, coronavirus, Mutation, Vaccines, VoC, B.1.351, COVID-19 pandemic, Genome, variant, spike glycoprotein, variants of concern, virus, Betacoronavirus, immune, Prevalence, South Africa, Transmissibility, Immune escape, B.1.1.7, P.1, trajectory, genetic variants, Genetic variant, pathogenicity, error, virulence, United Kingdom, binding, consensus sequence, Proofreading, Deleterious, Neutral, acute respiratory syndrome, Factor, host receptor, complex, new virus, RNA genome, genome replication, positive, polymerase, offer, driving, Effect, feature, genetic modification, new SARS-CoV-2, Wuhan, China, analyzed, identify, replicate, structural property, positive-sense single-stranded RNA, SARS-CoV-2 gene, the SARS-CoV-2 genome, 【제목키워드】 Dynamics, emergence,