Structural basis and mode of action for two broadly neutralizing antibodies against SARS-CoV-2 emerging variants of concern

Wenwei Li, Yaozong Chen, Jérémie Prévost, Irfan Ullah, Maolin Lu, Shang Yu Gong, Alexandra Tauzin, Romain Gasser, Dani Vézina, Sai Priya Anand, Guillaume Goyette, Debashree Chaterjee, Shilei Ding, William D. Tolbert, Michael W. Grunst, Yuxia Bo, Shijian Zhang, Jonathan Richard, Fei Zhou, Rick K. HuangLothar Esser, Allison Zeher, Marceline Côté, Priti Kumar, Joseph Sodroski, Di Xia, Pradeep D. Uchil, Marzena Pazgier*, Andrés Finzi*, Walther Mothes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Emerging variants of concern for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit more efficiently and partially evade protective immune responses, thus necessitating continued refinement of antibody therapies and immunogen design. Here, we elucidate the structural basis and mode of action for two potent SARS-CoV-2 spike (S)-neutralizing monoclonal antibodies, CV3-1 and CV3-25, which remain effective against emerging variants of concern in vitro and in vivo. CV3-1 binds to the (485-GFN-487) loop within the receptor-binding domain (RBD) in the “RBD-up” position and triggers potent shedding of the S1 subunit. In contrast, CV3-25 inhibits membrane fusion by binding to an epitope in the stem helix region of the S2 subunit that is highly conserved among β-coronaviruses. Thus, vaccine immunogen designs that incorporate the conserved regions in the RBD and stem helix region are candidates to elicit pan-coronavirus protective immune responses.

Original languageEnglish
Article number110210
JournalCell Reports
Volume38
Issue number2
DOIs
StatePublished - 11 Jan 2022
Externally publishedYes

Keywords

  • COVID-19
  • SARS-CoV-2
  • emerging variants of concern
  • epitopes
  • neutralizing antibodies
  • receptor-binding domain
  • β-coronaviruses

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