Preliminary report on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike mutation T478K

Abstract

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged, posing a renewed threat to coronavirus disease 2019 containment and to vaccine and drug efficacy. In this study, we analyzed more than 1,000,000 SARS-CoV-2 genomic sequences deposited up to April 27, 2021, on the GISAID public repository, and identified a novel T478K mutation located on the SARS-CoV-2 Spike protein. The mutation is structurally located in the region of interaction with human receptor ACE2 and was detected in 11,435 distinct cases. We show that T478K has appeared and risen in frequency since January 2021, predominantly in Mexico and the United States, but we could also detect it in several European countries.

Keywords: COVID-19; S:T478K; SARS-CoV-2; Spike; Spike:T478K; T478K; genomic surveillance.

Figure 1

(A) Prevalence of Spike mutation T478K in PANGO lineages. The top 10 lineages are reported, sorted by number of S:T478K samples over a total number of lineage samples. The discrete number of S:T478K is reported on top of each bar. Most S:T478K‐carrying samples are classified in the B.1.1.519 lineage. (B) Frequency of sequenced severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) genomes carrying the S:T478K mutation, divided into 10 years age ranges. The total number of S:T478K patients for the specified age range is reported on top of the bars. (C) Pie chart showing the distribution of S:T478K by patient sex. (D) Number of S:T478K samples over total samples sequenced from each country. The 10 countries with higher frequency (in percentage) are shown. Discrete numbers of S:T478K are reported on top of each bar. (E) Geographic global projection of S:T478K cases detected in each country. The color scale indicates the number of SARS‐CoV‐2 genomes carrying the S:T478K mutation, in logarithm‐10 scale

Figure 2

(A) Number of sequenced SARS‐CoV‐2 genomes carrying S:T478K mutation over time, measured weekly. (B) Prevalence over time of S:T478K in the SARS‐CoV‐2 population, measured as the number of S:T478K genomes over the total number of sequenced genomes. (C) Prevalence over time of S:N501Y in the SARS‐CoV‐2 population. (D) Prevalence over time of S:D614G in the SARS‐CoV‐2 population. SATRS‐CoV‐2, severe acute respiratory syndrome coronavirus 2

Figure 3

(A) 3D representation of the SARS‐CoV‐2 Spike/Human ACE2 interacting complex, derived from the crystal structure from. (B) Representation of the SARS‐CoV‐2 Spike electrostatic potential calculated with the Adaptive Poisson–Boltzmann Solver (APBS) program implemented in PyMOL. Molecular surface was colored according to the molecular electrostatic potential (ranging from −2.0 [red] to 2.0 [blue]) in T478 (reference, above) and in K478 (more recent mutation, below). (C) 3D detail of structural superposition of WT SARS‐CoV‐2 RBD and S:T478K. T478 side chains are colored in cyan, while K478 side chains are colored in red. ACE2, angiotensin‐converting enzyme 2; RBD, receptor‐binding domain; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; WT, wild‐type