Journal
BRIEFINGS IN BIOINFORMATICS
Volume 23, Issue 3, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bib/bbac045
Keywords
SARS-CoV-2; RNA; ORFs; Kozak sequence; proteomics; structures
Funding
- University of Ostrava [SGS01/P.rF/2020]
- VELUX Foundation [00014557]
- Novo Nordisk Foundation (BIO-MS)
- Wellcome Trust [200814/Z/16/Z]
- Antibiotic Research UK [PHZJ/687]
Ask authors/readers for more resources
This study investigates the potential existence of still undescribed SARS-CoV-2 proteins using sequence and structure-based bioinformatics methodologies. The findings suggest that there may be negative-sense ORFs in the SARS-CoV-2 genome that could play an important role in the viral lifecycle and COVID-19 pathogenesis.
SARS-CoV-2 is a novel positive-sense single-stranded RNA virus from the Coronaviridae family (genus Betacoronavirus), which has been established as causing the COVID-19 pandemic. The genome of SARS-CoV-2 is one of the largest among known RNA viruses, comprising of at least 26 known protein-coding loci. Studies thus far have outlined the coding capacity of the positive-sense strand of the SARS-CoV-2 genome, which can be used directly for protein translation. However, it has been recently shown that transcribed negative-sense viral RNA intermediates that arise during viral genome replication from positive-sense viruses can also code for proteins. No studies have yet explored the potential for negative-sense SARS-CoV-2 RNA intermediates to contain protein-coding loci. Thus, using sequence and structure-based bioinformatics methodologies, we have investigated the presence and validity of putative negative-sense ORFs (nsORFs) in the SARS-CoV-2 genome. Nine nsORFs were discovered to contain strong eukaryotic translation initiation signals and high codon adaptability scores, and several of the nsORFs were predicted to interact with RNA-binding proteins. Evolutionary conservation analyses indicated that some of the nsORFs are deeply conserved among related coronaviruses. Three-dimensional protein modeling revealed the presence of higher order folding among all putative SARS-CoV-2 nsORFs, and subsequent structural mimicry analyses suggest similarity of the nsORFs to DNA/RNA-binding proteins and proteins involved in immune signaling pathways. Altogether, these results suggest the potential existence of still undescribed SARS-CoV-2 proteins, which may play an important role in the viral lifecycle and COVID-19 pathogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available