SARS-CoV-2 one year on: evidence for ongoing viral adaptation

Abstract

SARS-CoV-2 is thought to have originated in the human population from a zoonotic spillover event. Infection in humans results in a variety of outcomes ranging from asymptomatic cases to the disease COVID-19, which can have significant morbidity and mortality, with over two million confirmed deaths worldwide as of January 2021. Over a year into the pandemic, sequencing analysis has shown that variants of SARS-CoV-2 are being selected as the virus continues to circulate widely within the human population. The predominant drivers of genetic variation within SARS-CoV-2 are single nucleotide polymorphisms (SNPs) caused by polymerase error, potential host factor driven RNA modification, and insertion/deletions (indels) resulting from the discontinuous nature of viral RNA synthesis. While many mutations represent neutral 'genetic drift' or have quickly died out, a subset may be affecting viral traits such as transmissibility, pathogenicity, host range, and antigenicity of the virus. In this review, we summarise the current extent of genetic change in SARS-CoV-2, particularly recently emerging variants of concern, and consider the phenotypic consequences of this viral evolution that may impact the future trajectory of the pandemic.

Keywords: COVID-19; SARS-CoV-2; adaptation; coronavirus; mutant; pandemic.

Fig. 1.

Genome organisation of SARS-CoV-2 with regions of interest annotated. Mutations of interest (for example those found in B.1.1.7) shown as both nucleotide and amino acid changes. Figure made using Biorender (https://biorender.com/).

Fig. 2.

Spike mutations of interest mapped to the spike trimer. Mutations shown in red, ACE2 shown in yellow, spike monomer in RBD ‘up’ conformation shown in green, spike monomers in RBD ‘down’ conformation shown in pink and blue. Structure made using PyMOL using PDBID 7A94 [24].