Mutational sensitivity of D614G in spike protein of SARS-CoV-2 in Jordan

Abstract

Background: Spike protein is the surface glycoprotein of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) necessary for the entry of the virus via the transmembrane receptors of the human respiratory cells causing COVID-19 disease.

Aim: Here, we aimed to predict the three-dimensional monomer structure of spike protein of SARS-CoV-2 from 20 Jordanian nasopharyngeal samples and to determine the percentage of single amino acid variants (SAV) in the spike protein of SARS-CoV-2.

Methods: The output of the Protein Homology/analogY Recognition Engine V 2.0 (Phyre2) found four single amino acid variants in the spike gene.

Results: The first variant represented by 5% of samples that showed tyrosine deletion at Y144 located in the N terminal domain. The second and the dominant variant, represented by 62%, showed aspartate a coil amino acid substitution to glycine an extracellular amino acid at D614G located in the spike recognition binding site. The third variant, represented by 5%, showed aspartate substitution to tyrosine at D1139Y, and the fourth variant, represented by 5% glycine substitution to serine at G1167S.

Conclusion: Our results have shown low mutational sensitivity in all variants except to D614G the one with the most likely neutral mutational sensitivity that all variants might not explicitly affect the function of spike glycoprotein. However, D614G might change the viral conformational plasticity and hence a potential viral fitness gain but one must be cautious about drawing any concrete conclusions about the severity of symptoms and viral transmission from genomic data only.

General significance: Studying mutations such as D614G in deep is essential to control the pandemic in terms of immune systems, antibodies, or even vaccines.

Keywords: COVID-19; D614G & Mutation; SARS-CoV-2; Spike.

Fig. 1

Spike protein secondary structure by position-specific scoring matrices (PSIPRED). The upper box shows the wild type D614 as a coil amino acid in light green color, and the lower box shows the G614 as an extracellular amino acid in orange color. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

(a) The final I-TASSER predicted spike glycoprotein spike protein monomer model, the PDB file is provided in the supplementary data, and (b) the trimer spike glycoprotein as elucidated by Cryo-EM; PDB:6vxx [19].

Fig. 3

Multiple Sequence Alignment showing Amino Acid Variant (SAV) viewed by Jalview. The blue arrow and the red box are just cursers; the white columns are the location of the SAV along the full length of the amino acid sequence of spike protein for 20 SARS-CoV-2 samples from Jordan. YP-009724390 is the reference sequence of the spike protein of from Wuhan. The number 1273 is the total number of amino acids in the line. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

(Phyre2) Mutational sensitivity (a) the locations of single amino acid variants del Y144 (left side) & D614G (right side) on spike protein as they have the highest mutation sensitivity scores. (b) The mutation sensitivity histograms for all four single amino acid variants on spike protein.