7MMO

LY-CoV1404 neutralizing antibody against SARS-CoV-2

Summary for 7MMO

• Entry DOI: 10.2210/pdb7mmo/pdb
• Descriptor: LY-CoV1404 Fab heavy chain, LY-CoV1404 Fab light chain, Spike protein S1, ... (5 entities in total)
• Functional Keywords: antibody neutralizing sars-cov-2, immune system, immune system-viral protein complex, immune system/viral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 140789.90

Authors

Hendle, J.,Pustilnik, A.,Sauder, J.M.,Coleman, K.A.,Boyles, J.S.,Dickinson, C.D. (deposition date: 2021-04-30, release date: 2021-05-12, Last modification date: 2024-10-23)

Primary citation

Westendorf, K.,Wang, L.,Zentelis, S.,Foster, D.,Vaillancourt, P.,Wiggin, M.,Lovett, E.,van der Lee, R.,Hendle, J.,Pustilnik, A.,Sauder, J.M.,Kraft, L.,Hwang, Y.,Siegel, R.W.,Chen, J.,Heinz, B.A.,Higgs, R.E.,Kallewaard, N.,Jepson, K.,Goya, R.,Smith, M.A.,Collins, D.W.,Pellacani, D.,Xiang, P.,de Puyraimond, V.,Ricicova, M.,Devorkin, L.,Pritchard, C.,O'Neill, A.,Dalal, K.,Panwar, P.,Dhupar, H.,Garces, F.A.,Cohen, C.,Dye, J.,Huie, K.E.,Badger, C.V.,Kobasa, D.,Audet, J.,Freitas, J.J.,Hassanali, S.,Hughes, I.,Munoz, L.,Palma, H.C.,Ramamurthy, B.,Cross, R.W.,Geisbert, T.W.,Menacherry, V.,Lokugamage, K.,Borisevich, V.,Lanz, I.,Anderson, L.,Sipahimalani, P.,Corbett, K.S.,Yang, E.S.,Zhang, Y.,Shi, W.,Zhou, T.,Choe, M.,Misasi, J.,Kwong, P.D.,Sullivan, N.J.,Graham, B.S.,Fernandez, T.L.,Hansen, C.L.,Falconer, E.,Mascola, J.R.,Jones, B.E.,Barnhart, B.C.
LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants.
Biorxiv, 2022

PubMed Abstract: SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization when administered early during COVID-19 disease. However, the emergence of variants of concern has negatively impacted the therapeutic use of some authorized mAbs. Using a high throughput B-cell screening pipeline, we isolated a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody called LY-CoV1404 (also known as bebtelovimab). LY-CoV1404 potently neutralizes authentic SARS-CoV-2 virus, including the prototype, B.1.1.7, B.1.351 and B.1.617.2). In pseudovirus neutralization studies, LY-CoV1404 retains potent neutralizing activity against numerous variants including B.1.1.7, B.1.351, B.1.617.2, B.1.427/B.1.429, P.1, B.1.526, B.1.1.529, and the BA.2 subvariant and retains binding to spike proteins with a variety of underlying RBD mutations including K417N, L452R, E484K, and N501Y. Structural analysis reveals that the contact residues of the LY-CoV1404 epitope are highly conserved with the exception of N439 and N501. Notably, the binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The breadth of reactivity to amino acid substitutions present among current VOC together with broad and potent neutralizing activity and the relatively conserved epitope suggest that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known variants causing COVID-19.

PubMed: 33972947
DOI: 10.1101/2021.04.30.442182

Experimental method

X-RAY DIFFRACTION (2.427 Å)