The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein

Abstract The SARS-CoV-2 Omicron/BA.1 lineage emerged in late 2021 and rapidly displaced the Delta variant before being overtaken itself globally by, the Omicron/BA.2 lineage in early 2022. Here, we describe how Omicron BA.1 and BA.2 show a lower severity phenotype in a hamster model of pathogenicity which maps specifically to the spike gene. We further show that Omicron is attenuated in a lung cell line but replicates more rapidly, albeit to lower peak titres, in human primary nasal cells. This replication phenotype also maps to the spike gene. Omicron spike (including the emerging Omicron lineage BA.4) shows attenuated fusogenicity and a preference for cell entry via the endosomal route. We map the altered…

• WT
  Wellcome Trust

  Awards: 206369/Z/17/Z, Z/17/Z
• IC
  Imperial College London
• UO
  University of Oxford
• UO
  University of Glasgow
• PI
  Pirbright Institute

  Award: BBS/E/I/00007038
• MR
  Medical Research Council

  Awards: BBS/E/I/00007038, MC_UU12014/2, MR/W005611/1
• BA
  Biotechnology and Biological Sciences Research Council

  Award: BBS/E/I/00007038