Potent neutralization of clinical isolates of SARS-CoV-2 D614 and G614 variants by a monomeric, sub-nanomolar affinity nanobody

Potent neutralization of clinical isolates of SARS-CoV-2 D614 and G614 variants by a monomeric, sub-nanomolar affinity nanobody

Abstract Despite unprecedented global efforts to rapidly develop SARS-CoV-2 treatments, in order to reduce the burden placed on health systems, the situation remains critical. Effective diagnosis, treatment, and prophylactic measures are urgently required to meet global demand: recombinant antibodie...

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Autores principales: Guillermo Valenzuela Nieto, Ronald Jara, Daniel Watterson, Naphak Modhiran, Alberto A. Amarilla, Johanna Himelreichs, Alexander A. Khromykh, Constanza Salinas-Rebolledo, Teresa Pinto, Yorka Cheuquemilla, Yago Margolles, Natalia López González del Rey, Zaray Miranda-Chacon, Alexei Cuevas, Anne Berking, Camila Deride, Sebastián González-Moraga, Héctor Mancilla, Daniel Maturana, Andreas Langer, Juan Pablo Toledo, Ananda Müller, Benjamín Uberti, Paola Krall, Pamela Ehrenfeld, Javier Blesa, Pedro Chana-Cuevas, German Rehren, David Schwefel, Luis Ángel Fernandez, Alejandro Rojas-Fernandez
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
Medicine
R
Science
Q
Acceso en línea:https://doaj.org/article/ee67da82c4154da782d61078ae559f70
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Sumario:Abstract Despite unprecedented global efforts to rapidly develop SARS-CoV-2 treatments, in order to reduce the burden placed on health systems, the situation remains critical. Effective diagnosis, treatment, and prophylactic measures are urgently required to meet global demand: recombinant antibodies fulfill these requirements and have marked clinical potential. Here, we describe the fast-tracked development of an alpaca Nanobody specific for the receptor-binding-domain (RBD) of the SARS-CoV-2 Spike protein with potential therapeutic applicability. We present a rapid method for nanobody isolation that includes an optimized immunization regimen coupled with VHH library E. coli surface display, which allows single-step selection of Nanobodies using a simple density gradient centrifugation of the bacterial library. The selected single and monomeric Nanobody, W25, binds to the SARS-CoV-2 S RBD with sub-nanomolar affinity and efficiently competes with ACE-2 receptor binding. Furthermore, W25 potently neutralizes SARS-CoV-2 wild type and the D614G variant with IC50 values in the nanomolar range, demonstrating its potential as antiviral agent.

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