Notable sequence homology of the ORF10 protein introspects the architecture of SARS-COV-2

Abstract

The global public health is endangered due to COVID-19 pandemic, which is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Despite having similar pathology to MERS and SARS-CoV, the infection fatality rate of SARS-CoV-2 is likely lower than 1%. SARS-CoV-2 has been reported to be uniquely characterized by the accessory protein ORF10, which contains eleven cytotoxic T lymphocyte (CTL) epitopes of nine amino acids length each, across various human leukocyte antigen (HLA) subtypes. In this study, all missense mutations found in sequence databases were examined across twnety-two unique SARS-CoV-2 ORF10 variants that could possibly alter viral pathogenicity. Some of these mutations decrease the stability of ORF10, e.g. I4L and V6I were found in the MoRF region of ORF10 which may also possibly contribute to Intrinsic protein disorder. Furthermore, a physicochemical and structural comparative analysis was carried out on SARS-CoV-2 and Pangolin-CoV ORF10 proteins, which share 97.37% amino acid homology. The high degree of physicochemical and structural similarity of ORF10 proteins of SARS-CoV-2 and Pangolin-CoV open questions about the architecture of SARS-CoV-2 due to the disagreement of these two ORF10 proteins over their sub-structure (loop/coil region), solubility, antigenicity and change from the strand to coil at amino acid position 26, where tyrosine is present. Altogether, SARS-CoV-2 ORF10 is a promising pharmaceutical target and a protein which should be monitored for changes which correlate to change pathogenesis and clinical course of COVID-19 infection.

Computational Analysis of SARS-CoV-2 and SARS-Like Coronavirus Diversity in Human, Bat and Pangolin Populations

“…The absence of this stop codon in the pangolin (which exhibited synonymous mutations at the same locus) and SARS-CoV-2 viruses could result in a longer isoform of the ORF10 or fundamental changes in its function and expression levels. In a previous study of SARS-CoV-2 and pangolin-CoV genomes, position 26 was also identified as a region of population level variation from Tyr and His which significantly modifies the secondary structure of the coil region of the protein [52].…”

Characterization and structural prediction of the putative ORF10 protein in SARS-CoV-2

“…According to Hassan et al 2020, a MoRF was predicted to occur in residues 3-7. 12 A unique feature associated with MoRFs is their ability to exist in semi-disordered (i.e. flexible) states until binding, after which they can assume designated secondary structures.…”

“…The exact implications are unclear, but the ORF10 protein contains high numbers of promiscuous cytotoxic T lymphocyte (CTL) epitopes, primarily on the α-helix. 12,15 A recent study by Liu et al 2020 found that in severe cases of COVID-19, the ORF10 was overexpressed when compared against ORF10 expression levels in moderate cases. 16 If the ORF10 protein is synthesized, this may help to partially explain the nature behind severe cases of COVID-19.…”

“…12,13 The ORF10 protein also lacks significant levels of disorder; however, a short molecular recognition feature (MoRF) likely spans residues 3-7. 12 This protein is hydrophobic with the α-helix having been identified as a possible transmembrane (TM) helix as well. 14…”

Hacking The Diversity Of SARS-CoV-2 And SARS-Like Coronaviruses In Human, Bat And Pangolin Populations

“…The absence of this stop codon in the pangolin (which exhibited synonymous mutations at the same locus) and human adapted viruses could result in a longer isoform of the ORF10 or fundamental changes in its function and expression levels. In a previous study of SARS-CoV-2 and pangolin-CoV genomes, position 26 was also identified as a region of population level variation from Tyr and His which significantly modifies the secondary structure of the coil region of the protein [55].…”