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

Abstract

Found just upstream of the 3'-untranslated region in the SARS-CoV-2 genome is the putative ORF10 which has been proposed to encode for the hypothetical ORF10 protein. Even though current research suggests this protein is not likely to be produced, further investigations into this protein are still warranted. Herein, this study uses multiple bioinformatic programs to theoretically characterize and construct the ORF10 protein in SARS-CoV-2. Results indicate this protein is mostly ordered and hydrophobic with high protein-binding propensity, especially in the N-terminus. Although minimal, an assessment of twenty-two missense mutations for this protein suggest slight changes in protein flexibility and hydrophobicity. When compared against two other protein models, this study's model was found to possess higher quality. As such, this model suggests the ORF10 protein contains a β-α-β motif with a β-molecular recognition feature occurring as the first β-strand. Furthermore, this protein also shares a strong phylogenetic relationship with other putative ORF10 protein's in closely related coronaviruses. Despite not yielding evidence for the existence of this protein within SARS-CoV-2, this study does present theoretical examinations that can serve as platforms to drive additional experimental work that assess the biological relevance of this hypothetical protein in SARS-CoV-2.

The Potential of Eukaryotic Cell-Free Systems as a Rapid Response to Novel Zoonotic Pathogens: Analysis of SARS-CoV-2 Viral Proteins

“…Within our work we could show the synthesis of ORF10 in the presence of a signal peptide ( Figure 4 ). We also present oligomerization of ORF10 ( Figure 1B ) which correlates to previous work where it was hypothesized that ORF10 might oligomerize to form a pore for ion fluctuations co-localizing with other accessory proteins ( Schuster, 2020 ). The data seen in this study clearly show that the translation initiation was improved in the presence of a signal peptide.…”

“…Initial work on ORF10 identified epitopes for cytotoxic T lymphocytes and a possible alteration of SARS-CoV-2 pathogenicity by mutations in the ORF10 protein was described ( Hassan et al, 2021 ). Other studies reflected that the protein can be terminated prematurely but also read through was emphasized ( Pancer et al, 2020 ; Schuster, 2020 ). Within our work we could show the synthesis of ORF10 in the presence of a signal peptide ( Figure 4 ).…”

Structure and Function of Major SARS-CoV-2 and SARS-CoV Proteins

“…Out of which, ORF10 is the last one with 117 nucleotides and is positioned upstream of the 3ʹ-untranslated region (3ʹ-UTR) and downstream of N gene encoding a protein with the length of 38 amino acids. [210][211][212] The function of this protein is still unclear and it does not share similarity in sequence with any other known protein. Biochemical and functional characterization of this protein using different bioinformatics tools indicated this protein as highly ordered, thermally stable, hydrophobic protein possessing at least one transmembrane region.…”

Characterization and Structural Prediction of ORF10, ORF7b, ORF7a, ORF6, Membrane Glycoprotein, and Envelope Protein in SARS-CoV-2 Bangladeshi Variant through Bioinformatics Approach

“…Conserved regions of ORF7b, ORF7a and ORF6, membrane glycoprotein, and envelope protein could be playing a fundamental role in the assembly of particular proteins, formation of protein structure and/or generating virulent functions by facilitating precise protein interactions. Although, defining relationships between specific sequences is not entirely possible when based solely on sequence data [31]. We can predict that the proteins here are highly ordered as intrinsically disordered proteins have a tendency to be phosphorylated that leads to disorder-to-order along with order-to-disorder transitions [32].…”