In a recent Nature Communications article, researchers determined an alpaca-derived single domain antibody fragment, Ty1, targets the receptor-binding domain (RBD) of the SARS-CoV-2 spike, directly preventing ACE2 engagement; inhibiting SARS-CoV-2 from entering host cells.
What is a nanobody?
Nanobodies are single-domain antibodies derived from the variable regions of Camelidae atypical immunoglobulins. Camelidae (e.g., camels and llamas) possess fully functional antibodies that consist of only heavy chains. These tiny, single variable domains have full antigen-binding capacity and are very stable.
Why it’s important
Angiotensin-converting enzyme 2 (ACE-2) is a crucial protein on various cells' surface. The SARS-CoV-2 virus binds to ACE2, using its spike-like protein, like a key inserted into a lock, before the virus can enter and infect the cell. Hence, ACE2 acts as a cellular doorway for SARS-CoV-2.
Researchers from the Karolinska Institutet discovered that nanobodie Ty1 target the spike-like protein on the SARS-CoV-2 virus's surface. The alpaca-derived single domain antibody fragment Ty1 was found to have specific and high-affinity binding to the receptor-binding domain (RBD) of the SARS-CoV-2 spike through a multitude of methods, including neutralization assays, flow cytometry, immunofluorescence, cryo-EM.
At an early step of infection, neutralizing antibodies can prevent virus entry, protecting high-risk individuals from developing Covid-19. Showcasing that "Despite being approximately one-tenth of the size of a conventional antibody, they retain specificity and affinity similar to conventional antibodies, while being far easier to clone, express, and manipulate. They are readily expressed in bacteria in large quantities and show high thermal stability and solubility, making them easily scalable and cost-effective."
The scientists also suggest that nanobodies "can be used as a detection reagent in flow cytometry and immunofluorescence demonstrating its suitability as a research tool and for diagnostics."
Reference:
Hanke, L., Vidakovics, M. L. P., Sheward, D., Das, H., Schulte, T., Morro, A. M., ... & Murrell, B. (2020). An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction. Nature Communications