Article ; Online: Potent neutralization of clinical isolates of SARS-CoV-2 D614 and G614 variants by a monomeric, sub-nanomolar affinity nanobody.
2021 Volume 11, Issue 1, Page(s) 3318
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 ...
| 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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| MeSH term(s) | Angiotensin-Converting Enzyme 2/immunology ; Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Antibody Affinity/genetics ; COVID-19/immunology ; COVID-19/virology ; Camelids, New World/immunology ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Green Fluorescent Proteins/genetics ; HeLa Cells ; Humans ; Immunization ; Male ; Neutralization Tests ; Peptide Library ; Protein Binding/genetics ; SARS-CoV-2/chemistry ; SARS-CoV-2/immunology ; SARS-CoV-2/isolation & purification ; Single-Domain Antibodies/immunology ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology ; Transfection |
| Chemical Substances | Antibodies, Neutralizing ; Antibodies, Viral ; Peptide Library ; Single-Domain Antibodies ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Green Fluorescent Proteins (147336-22-9) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) |
| Language | English |
| Publishing date | 2021-02-08 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2615211-3 |
| ISSN | 2045-2322 ; 2045-2322 |
| ISSN (online) | 2045-2322 |
| ISSN | 2045-2322 |
| DOI | 10.1038/s41598-021-82833-w |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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