Spike protein modeling and single amino acid variant analysis might suggest reduced transmitability of SARS-CoV-2 in Jordan, Middle East (preprint)

ABSTRACT

Spike protein (approx. 180 kDa) is the surface glycoprotein of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) necessary for the interaction of the virus with human endothelial cell receptors on the cell membrane to be engulfed causing COVID-19 disease after binding with the angiotensin-converting enzyme 2 (ACE2) with an evident activation by type II transmembrane protease TMPRSS2 . Therefore, mutations and amino acid variants analysis are essential in characterizing the mechanism of binding of spike protein with its receptor, which totally gives insights on possibilities to design a peptide or nucleotide-based vaccine for COVID-19. Here, we employed Iterative Threading Assembly Refinement (I-TASSER) and Multiple Alignment using Fast Fourier Transform (MAFFT) to predict the three-dimensional structure and to analyze the amino acid variants for spike protein sequences of SARS-CoV-2 from GISAID database of samples collected from Jordan to try to find a justification for low number of confirmed COVID-19 in Jordan, Middle East. Our findings showed the molecules structurally close to the spike glycoprotein from the Enzyme Commission (EC) numbers and active sites included Isoleucyl-tRNA synthetase, Crystal structure of the tricorn protease (hydrolase); Crystal structure of the T. Thermophilus RNA polymerase holoenzyme (transferase); Crystal structure of the complex between pyruvate-ferredoxin oxidoreductase from Desulfovibrio africanus and pyruvate (oxidoreductase); and Reovirus core (virus). Our MAFFT findings showed that Four Amino Acid Variants (SAV) founded in 20 samples of SARS-CoV-2 were not conserved residues in spike glycoprotein. What is equal to 5% of samples showed tyrosine (polar) deletion at Y144 , 62% of samples showed aspartate (polar, acidic) substitution to glycine (nonpolar) at D614G, 5% of samples showed aspartate (polar, acidic) substitution to tyrosine (polar) at D1139Y and 5% of samples showed glycine (nonpolar) substitution to serine (polar) at G1167S respectively. By using Phyre2, our findings have shown lower sensitive mutational that cannot affect the pocket region or alpha and beta-sheet in all mutations except for D614G, which has the highest mutational sensitivity score (5 out of 9) indicating a bigger effect on the function of spike protein. This might suggest, in general, a reduced transmitability of SARS-CoV-2 in Jordan, Middle East. As the crystal structure of spike protein is not revealed yet, it was not possible to compare the predicted modes versus each other.