Molecular and computational analysis of spike protein of newly emerged omicron variant in comparison to the delta variant of SARS-CoV-2 in Iraq

Abstract

Background: The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has had a major impact on world health over the last 2 years. The emergence of SARS-CoV-2 variants, particularly concerning variants, may affect the virus's pathogenicity, transmissibility, and vaccines potency. Both delta and the omicron variants have been designated by WHO as variants of concern.

Methods and results: In this study, molecular techniques such as qPCR, conventional PCR, and sequencing were used to identify the first SARS-CoV-2 omicron variant that circulated in Iraq in January 2022. Bioinformatics and computational tools like phylogenetic analysis, predicted physical and chemical properties, stability, and molecular docking of the spike protein were used to compare the omicron with the delta variants. We found the receptor binding domain (RBD) and spike protein in omicron contain a greater number of hydrophobic amino acids compared to delta variant. We discovered a disorder-order conversion in RBD regions of the omicron variant, and this change may be important in terms of the effect of disordered residues/regions on spike protein stability and interaction with human angiotensin converting enzyme 2 (ACE2). Docking studies show that the omicron variant requires less energy to engage with ACE2, contributing to its higher binding affinity with human ACE2, consistent with more contagious transmission.

Conclusion: This is the first molecular study of the circulated omicron and delta variants in Iraq, showing that the omicron variant in Iraq had a higher affinity for ACE2 than the delta variant, which may lead to higher transmissibility.

Keywords: ACE2; COVID-19; Delta; Omicron; SARS-CoV-2.

Fig. 1

Phylogenetic SARS-CoV-2 variant analysis. The phylogenetic tree was constricted based on sequence date in GISAID data using the Nextstrain server (Nextclade tool). The color indicates the GISAID clades, the red circle indicates the Iraq SARS-CoV-2 variants. The delta variant hCoV-19/Iraq/Sulaimani-8/2021 clusters in (21J delta). The omicron variant, hCoV-19/Iraq/Sulaimani-1/2022, is clustered in 21K omicron. (Color figure online)

Fig. 2

A sequence alignment of the spike amino acid sequences of SARS-CoV-2 wild type, omicron, and delta variants discovered in Iraq. The yellow highlights indicate non synonymous mutations, and the green highlights indicate indel mutations. The red letters indicate the RBD amino acid, while the box indicates the RBM amino acid. The amino acids are numbered according to the Wuhan-Hu-1 wild type. (Color figure online)

Fig. 3

Homology modeling of the SARS-CoV-2 spike protein tetramer identified in Iraq. The homotrimer protein chains A, B, are shown in cartoons in yellow, cyan, and purple. The red color represents the locations of mutations shown in the surface representation. The blue color indicated the insertion mutation. The gray labels indicate shared mutation by the omicron and delta variants. A Homology modeling of the omicron spike protein hCoV-19/Iraq/Sulaimani-1/2022. B Homology modeling of the delta spike protein hCoV-19/Iraq/Sulaimani-11/2021. (Color figure online)

Fig. 4

Molecular docking of SARS-CoV-2 RBD-hACE2. The blue color represents human ACE2, and the green color represents RBD monomer. The red color represents the mutation in RBD. The gray labels indicate shared mutation by the omicron and delta variants. A The surface structure of the omicron RBD-ACE2 complex. B The surface structure of the delta RBD-ACE2 complex. C Cartoon of the omicron RBD-ACE2 complex, with the RBD subjected to 15 mutations. D The delta RBD-ACE2 complex represents the RBD with only two mutations. E The interacting amino acid residues are shown as lines in the docking of omicron RBD-ACE2, and the hydrogen bonding interactions are represented by purple dashed lines. F The interacting amino acid residues are shown as lines in the docking of delta RBD-ACE2, and the hydrogen bonding interactions are represented by purple dashed lines. (Color figure online)