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. Author manuscript; available in PMC: 2025 Apr 30.
Published in final edited form as: Structure. 2025 Feb 11;33(4):677–690.e5. doi: 10.1016/j.str.2025.01.019

Table 2.

Framework optimization of nanobodies generated against wildtype SARS-CoV-2 spike protein.

Original Mutation TM (°C) KD (M)

LaG21L69F Wildtype S1–8 74.0 3.8
Mutant S1–8L70F 83.0 3.2

Wildtype S1–28 66.0 0.6
Mutant S1–28L70F 77.5 0.09

Wildtype S1–36 66.5 0.2
Mutant S1–36L70F 76.0 undetectable

LaG16E91K Wildtype S1–40 57.0 undetectable
Mutant S1–40S89K 59.5 0.5

Wildtype S1-RBD-14 65.0 25
Mutant S1-RBD-14E89K 62.5 0.3

Wildtype S1-RBD-42 42.0,59.0 7.5
Mutant S1-RBD-42E88K 64.0 0.1

LaG24Q68K Wildtype S1–14 59.5 2.4
Mutant S1–14Q66K 61.0 1.7

Wildtype S1-RBD-31 68.5 0.2
Mutant S1-RBD-31Q67K 71.5 0.4

TM and KD values for wildtype S1–14, S1–28, S1–36 and S1-RBD-14 taken from Mast et al.2

Mutant nanobodies are the wildtype nanobodies incorporating the equivalent original mutation in column 1. (SPR and DSF data detailed in Figures S8S9).