Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the pathogen responsible for the COVID-19 pandemic. The D614G substitution appeared in the spike glycoprotein (SGP) of SARS-CoV-2 at an early stage of the COVID-19 outbreak and the mutant carrying the substitution quickly became the most prevalent SARS-CoV-2 variant at several COVID-19 epicenters across the world. There has been a debate on the nature of the mutation, some even suggesting that the mutation is likely to be functionally neutral. One of the ways to understand the nature of this mutation is to study the evolutionary history of the 614th amino acid position of the spike glycoprotein in coronaviruses. In the present bioinformatics study we analyzed a few hundred SARS-CoV (of 2003 outbreak), SARS-CoV-2 and animal SARS-Like strains of the Sarbecovirus group to obtain insights into the conservation of aspartic acid at the 614th amino acid position in the SGP of these viruses, using our software tool Compare. After analyzing the conservation profiles of several Sarbecovirus sequences obtained from GenBank we show here that the 614 amino acid residue is located in an 11-amino acid densely hydrophobic motif, vavlyqdvnct (11-aa) that is almost perfectly conserved in the Sarbecovirus sub-genus and the D614G substitution increased the hydrophobicity of the motif by about 38%. We also identified one SARS-CoV genome in the pre-pandemic GenBank records (Accession: FJ882963) that has the D614G substitution. The fact that the original strain of SARS-CoV-2 with aspartic acid at the 614th position (D-variant) is now almost extinct emphasizes the importance of the D614G mutation for the survival of the virus. We propose that the D614G substitution altered the chemistry of the 11-aa and helped in the spread and continued survival of the virus by some yet to be identified biochemical mechanisms.
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