Functional mutations of SARS-CoV-2: implications to viral transmission, pathogenicity and immune escape

Abstract

The pandemic of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to major public health challenges globally. The increasing viral lineages identified indicate that the SARS-CoV-2 genome is evolving at a rapid rate. Viral genomic mutations may cause antigenic drift or shift, which are important ways by which SARS-CoV-2 escapes the human immune system and changes its transmissibility and virulence. Herein, we summarize the functional mutations in SARS-CoV-2 genomes to characterize its adaptive evolution to inform the development of vaccination, treatment as well as control and intervention measures.

Figure 1

Mutation hotspots of the reported VOIs and VOCs on the S protein. S protein mutations include G339D, S371L/F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, and L981F. The amino acid positions were determined according to reference sequence, Wuhan-Hu-1 (NC_045512.2). CTD: C-terminal domain; NTD: N-terminal domain; HR: Heptad repeat; RBD: Receptor binding domain; VOC: Variant of concern; VOI: Variant of interest.