Researchers in the UK have shown that llama-derived antibodies (Nanobodies) neutralize the SARS-CoV-2 virus in laboratory tests. The peer-reviewed survey results are Natural structure and molecular biology.
Llama, camels and alpaca can naturally produce large amounts of smaller antibodies with simpler structures and turn them into Nanobodies. The researchers designed a nanobody using a naiverama single-domain antibody library and polymerase chain reaction-based maturation, and used the purified receptor binding domain (RBD) of the SARS-CoV-2 spike to in vitro phage display. Technology has identified its binding partner.
This study reports the identification and characterization of two closely related high-affinity Nanobodies (H11-D4 and H11-H4) that blocked spike attachment to angiotensin converting enzyme 2 (ACE2) in vitro. ..
Using advanced X-ray and electron imaging, the team confirmed that Nanobodies bind to spike proteins differently than other newly discovered antibodies. Both Nanobodies inhibited both RBD and spike binding to ACE2. This suggests that the Nanobody epitope overlaps with the ACE2 binding site on the spike RBD.
Both Nanobodies neutralize live virus when fused to immunoglobulin G Fc, with H11-H4-Fc showing particularly high potency (50% neutralizing dose 4-6 nM). H11-H4 also showed additive neutralization by CR3022.
The Nanobodies may be applied by themselves or in additive combination with other antibodies in the treatment of severe COVID-19 patients, the researchers said.
Research professor James Naismith, professor of structural biology at Oxford University and director of the Rosalind Franklin Institute, said: “These Nanobodies could be used in a similar way to convalescent sera and disease. We can see that one of the Nanobodies can be combined with human antibodies, and that the combination is even more potent than either. I was able to show it.”
Huo J, Le Bas A, Ruza RR, Duyvesteyn HME, Mikolajek H, Malinauskas T, Tan TK, Rijal P, Dumuux M, Ward PN, Ren J, Zhou D, Harrison PJ, Weckener M, Clare DK, Vogirala VK, Radecke. J, Moynié L, Zhao Y, Gilbert-Jaramillo J, Knight ML, Tree JA, Butttigieg KR, Coombes N, Elmore MJ, Carroll MW, Carrique L, Shah PNM, James W, Townsend AR, Stuart DI, Owens RJ, Naismith JH. .. Neutralizing Nanobodies bind to the SARS-CoV-2 spike RBD and block its interaction with ACE2. Nat Struct Mol Biol. July 13, 2020 [Epub ahead of print].. Doi: 10.1038 / s41594-020-0469-6. PMID: 32661423.. Full text.
This article was first published Unibadis, It is part of the Medscape Professional Network.
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