Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant

We report that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta spike mutation P681R plays a key role in the Alpha-to-Delta variant replacement during the coronavirus disease 2019 (COVID-19) pandemic. Delta SARS-CoV-2 efficiently outcompetes the Alpha variant in human lung epithelial cells and primary human airway tissues. The Delta spike mutation P681R is located at a furin cleavage site that separates the spike 1 (S1) and S2 subunits. Reverting the P681R mutation to wild-type P681 significantly reduces the replication of the Delta variant to a level lower than the Alpha variant. Mechanistically, the Delta P681R mutation enhances the cleavage of the full-length spike to S1 and S2, which…

• WF
  Welch Foundation

  Award: AU-0042-20030616
• AG
  Amon G. Carter Foundation
• CP
  Cancer Prevention and Research Institute of Texas

  Awards: RP150551, RP190561, AI153602, R24 AI120942, 1R21AI145400
• JS
  John S. Dunn Foundation
• GL
  Gillson Longenbaugh Foundation
• RJ
  Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation
• SG
  Summerfield G. Roberts Foundation
• NI
  National Institutes of Health

  Awards: HHSN272201600013C, U01AI151801, UL1TR001439