This molecular modelling study has identified a new type of ganglioside-binding domain in the NTD of the SARS-CoV-2 S protein. This ganglioside-binding domain consists of a large flat interface enriched in aromatic and basic amino acid residues. It covers a stretch of 52 amino acid residues (111–162), which is longer than all linear ganglioside-binding domains characterized to date [29]. However, the new SARS-CoV-2 motif is organized into three distinct regions, including a central aromatic domain and two terminal basic domains (Fig. 10). Thus, this motif displays the typical features that determine optimal binding to gangliosides (i.e. CH-π stacking and electrostatic interactions).