Details

Autor(en) / Beteiligte

• Hernandez, Nancy E.
• Jankowski, Wojciech
• Frick, Rahel
• Kelow, Simon P.
• Lubin, Joseph H.
• Simhadri, Vijaya
• Adolf-Bryfogle, Jared
• Khare, Sagar D.
• Dunbrack, Roland L.
• Gray, Jeffrey J.
• Sauna, Zuben E.

Titel

Computational design of nanomolar-binding antibodies specific to multiple SARS-CoV-2 variants by engineering a specificity switch of antibody 80R using RosettaAntibodyDesign (RAbD) results in potential generalizable therapeutic antibodies for novel SARS-CoV-2 virus

Ist Teil von

• Heliyon, 2023-04, Vol.9 (4), p.e15032-e15032, Article e15032

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The human infectious disease COVID-19 caused by the SARS-CoV-2 virus has become a major threat to global public health. Developing a vaccine is the preferred prophylactic response to epidemics and pandemics. However, for individuals who have contracted the disease, the rapid design of antibodies that can target the SARS-CoV-2 virus fulfils a critical need. Further, discovering antibodies that bind multiple variants of SARS-CoV-2 can aid in the development of rapid antigen tests (RATs) which are critical for the identification and isolation of individuals currently carrying COVID-19. Here we provide a proof-of-concept study for the computational design of high-affinity antibodies that bind to multiple variants of the SARS-CoV-2 spike protein using RosettaAntibodyDesign (RAbD). Well characterized antibodies that bind with high affinity to the SARS-CoV-1 (but not SARS-CoV-2) spike protein were used as templates and re-designed to bind the SARS-CoV-2 spike protein with high affinity, resulting in a specificity switch. A panel of designed antibodies were experimentally validated. One design bound to a broad range of variants of concern including the Omicron, Delta, Wuhan, and South African spike protein variants. •· Identification of well characterized antibodies that bind to SARS-CoV-1 but not to SARS-CoV-2.•The use of RosettaAntibodyDesign to design variants of the anti-SARS-CoV-1 antibodies bind to SARS-CoV-2 with high affinity.•Experimental validation of the antibodies designed in silico.