ACE2 and infection: Given their essential role in cellular infection, the enhanced fitness observed in many SARS-CoV-2 variants have therefore been attributed primarily to mutations of the S-protein that dramatically increase both ACE2 and HS binding properties17 (Fig. 1c-e) by increasing the total formal charge of the trimeric S-protein (residues 13-1140) from + 3 (Wuhan) to + 18 and to + 24 for Delta B.1.617.2 and the Omicron B.1.1.529 subvariant, respectively18.