ACE2 and infection: As H2L represents a highly-accessible chemical scaffold that disrupts RBD-ACE2 interactions regardless of SARS-CoV-2 variant sequence and with selectivity over unrelated ligand–receptor interactions such as PD-1-PD-L1, additional studies are therefore warranted to assess H2L analogues for their ability to inhibit SARS-CoV-2 variant entry and replication using in vitro cellular infection models.