The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The COVID-19 pandemic is driven by the constant emergence of SARS-CoV-2 variants of concern (VOC), which exhibit increased transmissibility and/or increased evasion from neutralizing antibodies as compared to previously circulating viruses. The SARS-CoV-2 spike (S) protein engages the cellular receptor ACE2 for viral entry into host cells and augmented transmissibility of VOC might in part result from increased ACE2 binding. Further, neutralizing antibodies target the S protein/ACE2 interface and mutations in the S proteins of VOC can allow for evasion of neutralizing antibodies induced upon infection or vaccination. The latest VOC, the SARS-CoV-2 Omicron variant, emerged in winter 2021 and is now globally dominant. Several subvariants, BA.1, BA.2 and BA.3, of the Omicron variant have been identified but it is unclear whether they differ in host cell interactions and neutralization sensitivity. In addition, it is incompletely understood whether SARS-CoV-2 can enter target cells in an ACE2-independent fashion under certain conditions and whether this allows for evasion of neutralizing antibodies. Both questions will be addressed in my presentation.