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A broad neutralizing nanobody against SARS-CoV-2 engineered from an approved drug
- Source :
- Cell Death and Disease, Vol 15, Iss 6, Pp 1-9 (2024)
- Publication Year :
- 2024
- Publisher :
- Nature Publishing Group, 2024.
-
Abstract
- Abstract SARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain. Blocking this interaction has been proven to be an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody named VHH60, which was directly produced from an engineering nanobody library based on a commercialized nanobody within a very short period. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein at S351, S470-471and S493-494 as determined by structural analysis, with an affinity of 2.56 nM. It inhibits infections of both ancestral SARS-CoV-2 strain and pseudotyped viruses harboring SARS-CoV-2 wildtype, key mutations or variants at the nanomolar level. Furthermore, VHH60 suppressed SARS-CoV-2 infection and propagation 50-fold better and protected mice from death for twice as long as the control group after SARS-CoV-2 nasal infections in vivo. Therefore, VHH60 is not only a powerful nanobody with a promising profile for disease control but also provides evidence for a highly effective and rapid approach to generating therapeutic nanobodies.
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 15
- Issue :
- 6
- Database :
- Directory of Open Access Journals
- Journal :
- Cell Death and Disease
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.6d50b2d38bb4d22bdf8e9052c17481d
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41419-024-06802-7