Nanobodies

Our research focused on leveraging the unique properties of camelid-derived nanobodies to develop advanced diagnostic and therapeutic strategies for both amyloidogenic diseases and viral infections. In the field of amyloid inhibition, we have characterized nanobodies such as Nb24 and Nb23 that target highly amyloidogenic variants of β2-microglobulin (β2m), effectively hindering the protein self-aggregation associated with systemic amyloidosis. To understand these interactions at an atomic level, we utilized NMR spectroscopy and molecular dynamics to determine the solution structure of those nanobodies, identifying critical determinants like CDR3 loop flexibility and specific ionic interactions that govern their performance. 

We also applied a similar approach to characterize antiviral nanobodies, such as 2NSP23 and 2NSP90, that target the relatively invariant non-structural protein of SARS-CoV-2 Nsp9, a core component of the viral replication machinery. Our analysis revealed that these nanobodies act as a "structural lock" by stabilizing Nsp9 into a tetrameric state, which prevents its recruitment, as a monomer, within the replication transcription complex (RTC) and thus inhibits viral propagation. By employing advanced NMR techniques like the PENELOP methodology, we mapped Nsp9 epitopes.  

2NSP23 and 2NSP90 could be used as saliva-based quick diagnostics and variant-resistant antivirals in human or veterinary therapy because of the relative invariance of Nsp9 in different coronaviruses infecting various animal species.