Table 3.
Summary of X-ray crystallography, MST and TSA results for fragment hits targeting SARS-CoV-2 nsp110-126 and selected calculated properties. The ΔTi values of SARS-CoV-2 nsp110-126 in the presence of fragments obtained from nanoscale differential scanning fluorimetry (nanoDSF) and fragment affinities for SARS-CoV-2 nsp110-126 determined by MST are shown. TSA and MST experiments were conducted at least in triplicate. The Ti of SARS-CoV-2 nsp110-126 in the presence of 2.0% DMSO is 54.05 °C, which was used as a control in ΔTi calculations. The following chemical properties were calculated by Molsoft’s ICM Pro software [42]. MW, molecular weight; PSA, polar surface area; MollogP, calculated partition coefficient; HBA, hydrogen bond acceptor; HBD, hydrogen bond donor; MollogS, calculated solubility. *APUC: atypical protein unfolding curve.
| Fragment ID | Binding Site | MST Kd [mM] |
TSA Ti *± SD |
TSA ΔTi [°C] |
TSA |ΔTi|-3SD [°C] |
MW [Da] |
MolLogP (mol) |
HBA & HBD [No] |
mol PSA [Å2] |
MolLogS [Log(moles/L)] |
|---|---|---|---|---|---|---|---|---|---|---|
| 5E11 | I | 0.48 ± 0.30 | APUC | / | / | 203.1 | 2.75 | 1, 1 | 13.0 | −3.526 |
| 10B6 | I | 0.56 ± 0.19 | 51.27 ± 0.15 | −2.79 | 2.33 | 192.0 | 2.48 | 2, 3 | 48.4 | −3.495 |
| 11C6 | I | 1.16 ± 0.22 | 53.78 ± 0.05 | −0.27 | 0.13 | 238.0 | 2.73 | 2, 1 | 22.4 | −4.518 |
| 7H2 | II | >20 | 53.55 ± 0.25 | −0.50 | −0.25 | 155.1 | 1.23 | 1, 2 | 20.6 | −2.565 |
| 8E6 | II | 8.32 ± 3.32 | 52.72 ± 0.22 | −1.33 | 0.67 | 151.1 | 0.51 | 2, 2 | 28.8 | −0.603 |