7KMI
LY-CoV481 neutralizing antibody against SARS-CoV-2
Summary for 7KMI
Entry DOI | 10.2210/pdb7kmi/pdb |
Related | 7KMH |
Descriptor | LY-CoV481 Fab heavy chain, LY-CoV481 Fab light chain, Spike protein S1, ... (6 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 | 3 |
Total formula weight | 70081.99 |
Authors | Hendle, J.,Pustilnik, A.,Sauder, J.M.,Coleman, K.A.,Boyles, J.S.,Dickinson, C.D. (deposition date: 2020-11-02, release date: 2021-01-27, Last modification date: 2024-11-06) |
Primary citation | Jones, B.E.,Brown-Augsburger, P.L.,Corbett, K.S.,Westendorf, K.,Davies, J.,Cujec, T.P.,Wiethoff, C.M.,Blackbourne, J.L.,Heinz, B.A.,Foster, D.,Higgs, R.E.,Balasubramaniam, D.,Wang, L.,Zhang, Y.,Yang, E.S.,Bidshahri, R.,Kraft, L.,Hwang, Y.,Zentelis, S.,Jepson, K.R.,Goya, R.,Smith, M.A.,Collins, D.W.,Hinshaw, S.J.,Tycho, S.A.,Pellacani, D.,Xiang, P.,Muthuraman, K.,Sobhanifar, S.,Piper, M.H.,Triana, F.J.,Hendle, J.,Pustilnik, A.,Adams, A.C.,Berens, S.J.,Baric, R.S.,Martinez, D.R.,Cross, R.W.,Geisbert, T.W.,Borisevich, V.,Abiona, O.,Belli, H.M.,de Vries, M.,Mohamed, A.,Dittmann, M.,Samanovic, M.I.,Mulligan, M.J.,Goldsmith, J.A.,Hsieh, C.L.,Johnson, N.V.,Wrapp, D.,McLellan, J.S.,Barnhart, B.C.,Graham, B.S.,Mascola, J.R.,Hansen, C.L.,Falconer, E. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci Transl Med, 13:-, 2021 Cited by PubMed Abstract: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies are a key class of therapeutics that may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. Here, we report that high-throughput microfluidic screening of antigen-specific B cells led to the identification of LY-CoV555 (also known as bamlanivimab), a potent anti-spike neutralizing antibody from a hospitalized, convalescent patient with coronavirus disease 2019 (COVID-19). Biochemical, structural, and functional characterization of LY-CoV555 revealed high-affinity binding to the receptor-binding domain, angiotensin-converting enzyme 2 binding inhibition, and potent neutralizing activity. A pharmacokinetic study of LY-CoV555 conducted in cynomolgus monkeys demonstrated a mean half-life of 13 days and a clearance of 0.22 ml hour kg, consistent with a typical human therapeutic antibody. In a rhesus macaque challenge model, prophylactic doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract in samples collected through study day 6 after viral inoculation. This antibody has entered clinical testing and is being evaluated across a spectrum of COVID-19 indications, including prevention and treatment. PubMed: 33820835DOI: 10.1126/scitranslmed.abf1906 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.73 Å) |
Structure validation
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