LAUSR

The spike (S) protein of the SARS-CoV-2 Omicron variant is highly mutated but the impact of these mutations on viral entry into cells and its inhibition by antibodies has been unclear. A recent study published in Science by Mannar et al. now shows that these mutations are compatible with robust ACE2 binding and allow for ef fi cient evasion of neutralizing antibodies. The emergence of SARS-CoV-2 variants has become a hallmark of the COVID-19 pandemic. Variants of concern (VOC) harbor mutations in the viral S protein that can increase transmissibility, potentially by promoting S protein binding to the cellular receptor ACE2. Alternatively, mutations may alter epitopes of neutralizing antibodies, enabling the virus to infect convalescent or vaccinated individuals. The Delta variant dominated globally until the winter season 2021 when it was abruptly outcompeted by the emerging Omicron variant, which experienced an explosive global spread. Several features of the Omicron variant are incompletely understood, including its origin and the reason why the Omicron variant is less well able than the Delta variant to infect the lung and to cause severe disease. The Omicron S protein harbors at least 3 – 4 times more mutations than the S proteins of other VOCs and several of these mutations are known to reduce ACE2 binding. Mannar and coworkers these mutations are compensated by others, which establish new ACE2 contacts (Fig. 1a, b), resulting in overall robust ACE2 binding of the Omicron S protein (Fig. 1c). 1 Further, they show that mutations in the Omicron S protein confer ef fi cient evasion of antibody-mediated neutralization 1 In following fi