Highly synergistic combinations of nanobodies that target SARS-CoV-2 and are resistant to escape.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34874007.
- Also identified by DOI 10.7554/eLife.73027 and PMC identifier 8651292.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The emergence of SARS-CoV-2 variants threatens current vaccines and therapeutic antibodies and urgently demands powerful new therapeutics that can resist viral escape. We therefore generated a large nanobody repertoire to saturate the distinct and highly conserved available epitope space of SARS-CoV-2 spike, including the S1 receptor binding domain, N-terminal domain, and the S2 subunit, to identify new nanobody binding sites that may reflect novel mechanisms of viral neutralization. Structural mapping and functional assays show that indeed these highly stable monovalent nanobodies potently inhibit SARS-CoV-2 infection, display numerous neutralization mechanisms, are effective against emerging variants of concern, and are resistant to mutational escape. Rational combinations of these nanobodies that bind to distinct sites within and between spike subunits exhibit extraordinary synergy and suggest multiple tailored therapeutic and prophylactic strategies.
Medical subject headings
- COVID-19
- SARS-CoV-2
- Single-Domain Antibodies
- Spike Glycoprotein, Coronavirus