Could the severity of COVID-19 be enhanced by ORF10 accessory proteins?

ABSTRACT

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV2) has impacted human society, leading to dramatic changes in lifestyle. Similar outbreaks of other human coronaviruses including SARS-CoV and Middle East respiratory syndrome (MERS) coronavirus (MERS-HCoV) occurred in the past but were limited to certain regions of the world. The global spread of SARS-CoV2 was distinct from the other two outbreaks raising the question whether differences of this virus, in comparison to other human coronaviruses, could impact the nature of the spread. This study aimed to understand the genomic differences between the three viruses and made an effort to identify the protein coding regions in the genome and unique proteins likely to be expressed by SARS-CoV2 using various bioinformatics tools. The protein BLAST search found the ORF10 protein of SARS-CoV2 was absent in the other human coronaviruses. The nucleotide BLAST further supported the total absence of sequences encoding ORF10 in MERS-HCoV. Meanwhile, a similar region of nucleotides was identified in SARS-CoV but encoding a truncated ORF10 protein. Further analysis of the protein sequence using TargetP revealed the presence of a signal peptide in ORF10 indicating the ER/Golgi preprocessing of the protein. Interestingly, the protein sequence after the cleavage site contained hydrophobic regions indicating possible hydrophobic interactions. The secondary structure prediction of the amino acid sequences suggested a beta sheet structure after the cleavage site and the prediction of function using FFPred 3 algorithm revealed a possible role as membrane bound transport protein or signalling protein. These findings of uniqueness of ORF10 and predicted intrinsic characteristics support possible involvement of ORF10 protein in giving COVID-19 its specific characteristics like spread and virulence. Further investigations involving experimental studies to understand the role of ORF10 in disease pathogenesis is imperative to establish its role and could provide an intervention strategy to reduce the severity of COVID-19.