| Abstract: | Provided herein are asymmetric biparatopic neutralizing nanobody-based antibodies which engage SARS-2 spike in at least two independent epitopes. Several biparatopic constructs showed synergy in neutralizing viral infection of cells. Data also showed that single biparatopic constructs are more effective than the combination of the parental monotopic constructs were at neutralization. The nanobodies that were identified in an initial screen of a large and highly diverse library bind to a single epitope that overlaps with the ACE2 binding site. |