Tracking the amino acid changes of spike proteins across diverse host species of severe acute respiratory syndrome coronavirus 2

Abstract

Knowledge of the host-specific properties of the spike protein is of crucial importance to understand the adaptability of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to infect multiple species and alter transmissibility, particularly in humans. Here, we propose a spike protein predictor SPIKES incorporating with an inheritable bi-objective combinatorial genetic algorithm to identify the biochemical properties of spike proteins and determine their specificity to human hosts. SPIKES identified 20 informative physicochemical properties of the spike protein, including information measures for alpha helix and relative mutability, and amino acid and dipeptide compositions, which have shown compositional difference at the amino acid sequence level between human and diverse animal coronaviruses. We suggest that alterations of these amino acids between human and animal coronaviruses may provide insights into the development and transmission of SARS-CoV-2 in human and other species and support the discovery of targeted antiviral therapies.

Keywords: Association analysis; Bioinformatics; Virology.

Graphical abstract

Figure 1

System overview of SPIKES (A–D) (A) Collection of spike protein sequences, (B) preprocessing and feature extraction, (C) method in brief, and (D) the analysis of identified spike proteins between human and animal host coronaviruses.

Figure 2

The comparison of physicochemical properties The property comparison of spike protein between human and animal host coronaviruses (A) RACS820104, (B) ROBB760101, (C) RACS820109, (D) GEIM800105, and (E) JOND920102.

Figure 3

The helix core of spike protein (A and B) (A) Structures of post-fusion core of 2019-nCoV S2 subunit (PDB: 6LXT) and (B) post-fusion hairpin conformation of the SARS-CoV spike glycoprotein (PDB: 1WYY). Close-up view of helix core (HR1 domain) from the helix bundle and arrangement of amino acids shown as ball-and-stick model.

Figure 4

The comparison of mutations in spike protein across different variants of coronaviruses Spike glycoprotein (PDB: 6ACJ) in complex with ACE2 (green ribbon) and amino acid changes occurred between (A) hCoV-19/bat/Yunnan/Prc3/2018 and hCoV/Wuhan/WIV05/2019, (B) Delta strain VOC G/452R.V3 (B.1.617+) and hCoV-19/Wuhan/WIV04/2019, and (C) Alpha strain VOC 20212/01 GRY (B.1.17) and hCoV-19/Wuhan/WIV04/2019. The mutations in different strains are shown in color balls.

Figure 5

Recent variants emerging in SARS-CoV-2 (A) Top variants that are emerging with mutations in the spike protein. (B) Number of amino acid changes that occurred in the variants over the 3 months (March, April, and May 2021).

Figure 6

Compositional difference analysis (A and B) (A) Amino acid compositional difference between spike proteins of human and animal corona viruses and (B) dipeptide compositional differences between spike proteins of human and animal coronaviruses.

Figure 7

Surface hydrophobicity difference between PDB: 6VXX and 6ACC Secondary structure and surface hydrophobicity of (A) PDB: 6VXX and (B) PDB: 6ACC, respectively.