In silico evidence of superantigenic features in ORF8 protein from COVID-19

Abstract

Very early on COVID-19 pandemic outbreak, it was noted that the some of the virus-induced clinical conditions resembled features of toxaemia caused by the toxic shock syndrome toxin type 1, which is a soluble superantigen produced by Staphylococcus aureus. Among all SARS proteins, the ORF8 protein from SARS-2 virus is significantly different from other known SARS-like coronaviruses, and therefore could exhibit unique pathogenic properties. We assess if ORF8 protein bears super antigenic features using in silico tools. We show that ORF8 has properties of an extracellular soluble protein and shares a significant degree of amino acid sequence identity with toxic shock syndrome toxin. Besides, docking and binding affinity analyses between monomeric and homodimeric ORF-8 with Vβ 2.1 and TRBV11-2 reveal strong interaction and high binding affinity. ORF8-TRBV11-2 strong interaction can contribute to the observed clonal expansion of that chain during COVID-19-associated multisystem inflammatory syndrome. Taken together, the evidence presented here supports the hypothesis that ORF8 protein from SARS-2 bears super antigenic properties.

Superantigens and SARS-CoV-2

“…The issue of whether SARS-CoV-2 contains a superantigen is not settled, but the evidence is accumulating [90][91][92][93][94][95] and SARS-CoV-2 is causing superantigen or superantigenlike clinical presentations and biomarkers. In addition to cytokine storms [96], T-cell activation and deletion [74] and presentation of MIS-C [73,97,98] (similar to Kawasaki disease, a suspected consequence of superantigen exposure [99]), those infected by SARS-CoV-2 who suffer Long COVID following infection manifest symptoms [100] typically seen in autoimmune conditions such as SLE [101][102][103], and autoantibodies [71] and antinuclear antibodies [72] have been detected in a proportion of such individuals [104].…”