High Affinity Nanobodies Block SARS-CoV-2 Spike Receptor Binding Domain Interaction with Human Angiotensin Converting Enzyme

Published: July 24, 2020, 9:05 p.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.24.219857v1?rss=1 Authors: Esparza, T. J., Brody, D. L. Abstract: There are currently no approved effective treatments for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Nanobodies are 12-15 kDa single-domain antibody fragments that are more stable and amenable to large-scale production compared to conventional antibodies. Nanobodies can also be administered in an inhaled form directly to the lungs. We have isolated several nanobodies that bind to the SARS-CoV-2 spike protein receptor binding domain and block spike protein interaction with the angiotensin converting enzyme 2 (ACE2) receptor. The SARS-CoV-2 spike protein is responsible for viral entry into human cells via interaction with ACE2 on the cell surface. The lead therapeutic candidate, NIH-CoVnb-112, binds to the SARS-CoV-2 spike protein receptor binding domain at approximately 5 nM affinity, and blocks spike protein interaction with the human ACE2 receptor at approximately 0.02 micrograms/mL EC50 (1.1 nM). The affinity and blocking potency of NIH-CoVnb-112 are substantially better than previously reported candidate nanobody therapeutics for SARS CoV-2, and bind to a distinct site. Furthermore, NIH-CoVnb-112 blocks interaction between ACE2 and several high affinity variant forms of the spike protein. When multimerized or combined with other nanobodies, the effective affinity and blocking interactions may be even more potent, as has been well described for other nanobody therapeutics. These resulting nanobodies have therapeutic, preventative, and diagnostic potential. Copy rights belong to original authors. Visit the link for more info