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Compound class:
Antibody
Comment: CR3022 is a monoclonal antibody that binds Spike protein (S) of SARS-CoV and SARS-CoV-2 [2-3,5]. It was developed from a single chain Fv phage display library derived from lymphocytes from the convalescent plasma of a SARS-CoV patient, and reconstructed into IgG1 format [2]. CR3022 does not compete for binding with antibodies that bind to the ACE2 RBD of S, and acts allosterically to reduce binding to ACE2 [1]. Cryo-EM analysis shows that CR3022 Fab disrupts S conformation, so as to promote conversion to the fusion-incompetent post-fusion state, thus incapacitating the virus's ACE2-dependent infection mechanism [1]. Elucidating the protein-protein interactions that determine SARS-CoV-2/ACE2 binding and viral infection will help to identify ways in which this crucial interaction might the targeted for therapeutic development [4].
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
| References |
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1. Huo J, Zhao Y, Ren J, Zhou D, Duyvesteyn HME, Ginn HM, Carrique L, Malinauskas T, Ruza RR, Shah PNM et al.. (2020)
Neutralisation of SARS-CoV-2 by destruction of the prefusion Spike. Cell Host and Microbe, In press. DOI: 10.1016/j.chom.2020.06.010 |
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2. ter Meulen J, van den Brink EN, Poon LL, Marissen WE, Leung CS, Cox F, Cheung CY, Bakker AQ, Bogaards JA, van Deventer E et al.. (2006)
Human monoclonal antibody combination against SARS coronavirus: synergy and coverage of escape mutants. PLoS Med, 3 (7): e237. [PMID:16796401] |
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3. Tian X, Li C, Huang A, Xia S, Lu S, Shi Z, Lu L, Jiang S, Yang Z, Wu Y et al.. (2020)
Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microbes Infect, 9 (1): 382-385. [PMID:32065055] |
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4. Whisenant J, Burgess K. (2020)
Blocking Coronavirus 19 Infection via the SARS-CoV-2 Spike Protein: Initial Steps. ACS Med Chem Lett, 11 (6): 1076-1078. [PMID:32547694] |
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5. Yuan M, Wu NC, Zhu X, Lee CD, So RTY, Lv H, Mok CKP, Wilson IA. (2020)
A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV. Science, 368 (6491): 630-633. [PMID:32245784] |
