Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

Abstract The SARS-CoV-2 Omicron BA.1 variant emerged in 2021 1 and has multiple mutations in its spike protein 2 . Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower…

• HH
  Howard Hughes Medical Institute
• BW
  Burroughs Wellcome Fund
• BA
  Bill and Melinda Gates Foundation

  Awards: OPP1156262, INV-018944
• TS
  Takeda Science Foundation
• NB
  NHS Blood and Transplant

  Award: WPA15-02
• JA
  Japan Agency for Medical Research and Development

  Awards: 20fk0108163, CREST, 21fk0410033, 20fk0108146, 20fk0108413, 20wm0325009, 20fk0108451, 21wm0325009
• WT
  Wellcome Trust

  Awards: Z/17/Z, WT108082AIA, DEL-15-006, 207498, 207498/Z/17/Z
• TB
  Tokyo Biochemical Research Foundation
• UR
  UK Research and Innovation

  Award: MR/W005611/1
• FG
  Fast Grants
• NI
  National Institute for Health and Care Research

  Awards: RG94028, 207498, RG85445
• DO
  Department of Health and Social Care

  Award: HHSN272201700059C
• UO
  University of Cambridge
• NU
  Newcastle University
• RT
  Rosetrees Trust
• SA
  South African Medical Research Council

  Awards: 6084-CO-AP-2020, DEL-15-006
• MF
  Mitsubishi Foundation
• EA
  European Association for the Study of the Liver
• NI
  National Institutes of Health

  Awards: COVID-19, OPP1156262, HHSN272201700059C
• NB
  NIHR BioResource
• MR
  Medical Research Council

  Awards: MR/T032413/1, MR/P008801/1, MR/W005611/1, MC_PC_17230, MR/T032413/1, COVID-19
• EA
  Engineering and Physical Sciences Research Council

  Awards: EP/V002910/1, EP/V002910/1
• JS
  Japan Society for the Promotion of Science

  Awards: 18H02662, 18KK0447, JPJSCCA20190008, CREST, 21H02737, 19J20488, 19K06382
• RI
  Research Institute for Microbial Diseases, Osaka University
• NI
  National Institute of General Medical Sciences

  Award: 5T32GM008268
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: HHSN272201700059C, COVID-19, DP1AI158186, OPP1156262
• IO
  Institute of Genetics
• CR
  Core Research for Evolutional Science and Technology

  Award: JPMJCR20H4
• SI
  Strategic International Collaborative Research Program