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 amenable to inexpensive large-scale production and can be delivered by inhalation. We have isolated 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) with 1-5 nM affinity. The lead nanobody candidate, NIH-CoVnb-112, blocks SARS-CoV-2 spike pseudotyped lentivirus infection of HEK293 cells expressing human ACE2 with an EC50 of 0.3 micrograms/mL. NIH-CoVnb-112 retains structural integrity and potency after nebulization. Furthermore, NIH-CoVnb-112 blocks interaction between ACE2 and several high affinity variant forms of the spike protein. These nanobodies and their derivatives have therapeutic, preventative, and diagnostic potential.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Funding: National Institute of Neurological Disorders and Stroke (NINDS) Intramural Research Program, Uniformed Services University of the Health Sciences; National Institute of Environmental Health Sciences Intramural Research Program, Research Triangle Park, NC
Disclaimer: The views expressed in this manuscript reflect those of the authors, and not those of the Uniformed Services University of the Health Sciences or the Department of Defense.
additional data, analyses and discussion
