Recent report by Clausen et al. sheds light on the key role of HS in the SARS-CoV-2 binding to the ACE2 at the cell membrane.1 They revealed that HS interacts with residues, adjacent to the ACE2-binding site at the RBD of the S1 subunit of the SARS-CoV-2 trimeric S-protein, and this event, in turn, promotes the opening of S-protein conformation for ACE2 binding and thereby potentiates viral infection (Fig. 1b). The gene discussed is PROS1; the disease is viral infectious disease.