发布时间:
2021-05-11 00:00:00
期刊:
PNAS
doi: 10.1073/pnas.2101918118
作者:
Phillip Pymm,Amy Adair,Li-Jin Chan,James P. Cooney,Francesca L. Mordant,Cody C. Allison,Ester Lopez,Ebene R. Haycroft,Matthew T. O’Neill,Li Lynn Tan,Melanie H. Dietrich,Damien Drew,Marcel Doerflinger,Michael A. Dengler,Nichollas E. Scott,Adam K. Wheatley,Nicholas A. Gherardin,Hariprasad Venugopal,Deborah Cromer,Miles P. Davenport,Raelene Pickering,Dale I. Godfrey,Damian F. J. Purcell,Stephen J. Kent,Amy W. Chung,Kanta Subbarao,Marc Pellegrini,Alisa Glukhova,Wai-Hong Tham
摘要:
Neutralizing antibodies are important for immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and as therapeutics for the prevention and treatment of COVID-19. We identified high-affinity nanobodies against SARS-CoV-2 receptor-binding domain and found that nanobody cocktails consisting of two noncompeting nanobodies were able to block ACE2 engagement with RBD variants present in human populations and potently neutralize both wild-type SARS-CoV-2 and the N501Y D614G variant at low concentrations. Prophylactic administration of nanobody cocktails reduced viral loads in mice infected with the N501Y D614G SARS-CoV-2 virus, showing that nanobody cocktails are useful as prophylactic agents against SARS-CoV-2.
Cryo-EM maps for WNb 2 WNb 10 SARS-CoV-2 Spike complex are available in the the Electron Microscopy Data Bank (EMDB) ([EMD-23566][1]). The WNb 2 WNb 10 SARS-CoV-2 RBD co-ordinates are available in the Protein Data Bank (PDB) ([7LX5][2]). The WNb 2 SARS-CoV-2 RBD crystallography data are available in the Protein Data Bank (PDB) ([7LDJ][3]). All other study data are included in the article and/or [ SI Appendix ][4].
[1]: https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-23566
[2]: http://www.rcsb.org/pdb/explore/explore.do?structureId=7LX5
[3]: http://www.rcsb.org/pdb/explore/explore.do?structureId=7LDJ
[4]: https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2101918118/-/DCSupplemental