We recently discovered a superantigenic region on tSARS-CoV-2 spike, whose sequence and structure characteristics closely resemble those of a bacterial toxin, staphylococcal enterotoxin B (SEB), known to cause toxic shock syndrome (TSS) (1). The similarity between this region and SEB led us to hypothesize that (i) multisystem inflammatory syndrome (MIS) observed in children as well as adults with severe Covid-19, which shows same symptoms as TSS (2), could be caused by this region and (ii) anti-SEB monoclonal antibodies (mAbs) could be used for neutralizing this region. Among anti-SEB mAbs, we identified one, 6D3, that has been experimentally verified to reduce SARS-CoV-2 infectivity (3). Notably, this superantigenic region also includes the PRRA insert - the recognition site for proteases (TMPRSS2 or furin) essential to assist viral entry. The effective suppression of infectivity by 6D3 may be attributed to its blocking of the protease binding site (3). This study invites attention to the existence of alternative mAb binding sites, other than those on the RBD, which may be advantageously used in mAb cocktail treatments.

A superantigenic region that overlaps with proteolytic cleavage site of SARS-CoV-2 spike: A new target for monoclonal antibody binding

ACS Spring Meeting 2021

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