There are currently few 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 can be delivered by inhalation and are amenable to relatively inexpensive large scale production compared to other biologicals. 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 EC 50 of 0.3 µg/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.
【저자키워드】 Medical research, Biochemistry, Drug development, Proteins, 【초록키워드】 Treatment, SARS-CoV-2, ACE2, COVID-19 pandemic, angiotensin converting enzyme 2, variant, Infection, diagnostic, virus, angiotensin converting enzyme, Spike protein, Receptor binding domain, human ACE2, nanobody, lentivirus, therapeutic, inhalation, nanobodies, SARS-CoV-2 spike, Interaction, angiotensin, nebulization, lead, enzyme, SARS-CoV-2 spike protein receptor binding domain, high affinity, potency, derivative, HEK293 cells, pseudotyped, block, effective, responsible, form, approved, the spike protein, antibody fragment, expressing, HEK293 cell, the SARS-CoV-2, 【제목키워드】 angiotensin converting enzyme, Receptor binding domain, nanobody, SARS-CoV-2 spike, Interaction, enzyme,