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Cell Rep
. 2021 Dec 15;110210.
doi: 10.1016/j.celrep.2021.110210. Online ahead of print.
Structural basis and mode of action for two broadly neutralizing antibodies against SARS-CoV-2 emerging variants of concern
Wenwei Li 1 , Yaozong Chen 2 , Jérémie Prévost 3 , Irfan Ullah 4 , Maolin Lu 1 , Shang Yu Gong 5 , Alexandra Tauzin 3 , Romain Gasser 3 , Dani Vézina 3 , Sai Priya Anand 5 , Guillaume Goyette 6 , Debashree Chaterjee 6 , Shilei Ding 6 , William D Tolbert 2 , Michael W Grunst 1 , Yuxia Bo 7 , Shijian Zhang 8 , Jonathan Richard 3 , Fei Zhou 9 , Rick K Huang 9 , Lothar Esser 9 , Allison Zeher 9 , Marceline Côté 7 , Priti Kumar 4 , Joseph Sodroski 8 , Di Xia 9 , Pradeep D Uchil 1 , Marzena Pazgier 10 , Andrés Finzi 11 , Walther Mothes 12
Affiliations
- PMID: 34971573
- DOI: 10.1016/j.celrep.2021.110210
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.
Keywords: COVID-19; SARS-CoV-2; emerging variants of concern; epitopes; neutralizing antibodies; receptor-binding domain; β-coronaviruses.