Slaying SARS-CoV-2 One (Single-domain) Antibody at a Time

• Published in: Trends in Microbiology 2021-03, Vol.29 (3), p.195-203
• Main Authors: Czajka, Timothy F., Vance, David J., Mantis, Nicholas J.
• Format: Article
• Language: English
• Subjects: Affinity; Antibodies; Antibodies, Viral - chemistry; Antibodies, Viral - immunology; Antibody libraries; Avidity; Binding; Coronaviruses; COVID-19; Domains; Humans; Nanobodies; Opinion; Phages; Protein Structure, Tertiary; Severe acute respiratory syndrome coronavirus 2; Single-Domain Antibodies - chemistry; Single-Domain Antibodies - immunology; Spike Glycoprotein, Coronavirus - immunology; Spike protein; Synthetic Biology - methods; Yeasts
• ISSN: 0966-842X; 1878-4380
• DOI: 10.1016/j.tim.2020.12.006

Camelid-derived and synthetic single-domain antibodies (sdAbs) are emerging as potent weapons against the novel coronavirus, SARS-CoV-2. sdAbs are small, compact, thermostable immunoglobulin elements capable of binding targets with subnanomolar affinities. By leveraging the power of phage- and yeast surface-display technologies, rare sdAbs can be isolated from highly diverse and complex antibody libraries. Once in hand, sdAbs can be engineered to improve binding affinity, avidity, target specificities, and biodistribution. In this Opinion piece we highlight a series of sophisticated studies describing the identification of ultrapotent sdAbs directed against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. We discuss the possible applications of these antibodies in the global fight against COVID-19. sdAbs are small, thermostable immunoglobulin elements that were first discovered in camels.Recent reports describe the isolation of sdAbs specific to the novel coronavirus, SARS-CoV-2, using phage- and yeast-display libraries.sdAbs with SARS-CoV-2 neutralizing activity target the trimeric Spike protein and block entry of the virus into host cells.Ultrapotent sdAbs have broad applications as antivirals and diagnostics in the fight against COVID-19.