Multiple Protein Isoforms with Isoelectric Point in the Blood pH Physiological Range May Underpin High Virulence and Pathogenicity of SARS-CoV-2 B1617 Strain

Genome sequencing has ushered a new era in modern biology by allowing scientists to investigate the assembled genome for clues on pathogenic potential as well as new and emerging virulent genes in the genome. This work started out with the validation of an in-house MATLAB gene finder software that examined the SARS-CoV-2 B1617 strain assembled genome. Data reveals 70 open reading frames, whose calculated molecular weight and isoelectric point yields a theoretical protein 2D gel electrophoresis pattern with clustering of high molecular weight proteins (i.e., 50 to 300 kDa) within the physiological pH range of 6 to 8. Such results suggest one possible reason for the high virulence of SARS-CoV-2 B1617 strain due probably to the pathogenic effects of the high molecular weight proteins that have isoelectric point in the pH 6 to 8 window. Further observations of clusters of proteins with closely similar number of amino acids in the range of 200 to 300, 1300 to 1400, 1800 to 1900, 1900 to 2000, and 2000 to 2100 prompted the development of another in-house MATLAB multiple sequence alignment software. Results from the alignment reveals that, in each protein cluster, there are one or two more ancient proteins with long N-terminal end that is not present in the modern version of the protein, which share long segment of high sequence conservation with the ancient proteins after the N-terminal end segment. This shows that SARS-CoV-2 B1617 strain may be evolutionary ancient, and relics of ancient proteins are still remnants in the assembled genome of the virus strain. Overall, this work unexpectedly highlights salient features of SARS-CoV-2 B1617 strain as having high molecular weight proteins with isoelectric points in the pH 6 to 8 physiological window, as well as the virus harbouring ancient proteins with unknown pathogenic and virulence potential.