| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T3 |
0-112 |
Sentence |
denotes |
Structure-based stabilization of protein–protein interactions (PPIs) is a promising strategy for drug discovery. |
| T4 |
113-247 |
Sentence |
denotes |
However, this approach has mainly focused on the stabilization of native PPIs, and non-native PPIs have received little consideration. |
| T5 |
248-425 |
Sentence |
denotes |
Here, we identified a non-native interaction interface on the three-dimensional dimeric structure of the N-terminal domain of the MERS-CoV nucleocapsid protein (MERS-CoV N-NTD). |
| T6 |
426-515 |
Sentence |
denotes |
The interface formed a conserved hydrophobic cavity suitable for targeted drug screening. |
| T7 |
516-747 |
Sentence |
denotes |
By considering the hydrophobic complementarity during the virtual screening step, we identified 5-benzyloxygramine as a new N protein PPI orthosteric stabilizer that exhibits both antiviral and N-NTD protein-stabilizing activities. |
| T8 |
748-1015 |
Sentence |
denotes |
X-ray crystallography and small-angle X-ray scattering showed that 5-benzyloxygramine stabilizes the N-NTD dimers through simultaneous hydrophobic interactions with both partners, resulting in abnormal N protein oligomerization that was further confirmed in the cell. |
| T9 |
1016-1175 |
Sentence |
denotes |
This unique approach based on the identification and stabilization of non-native PPIs of N protein could be applied toward drug discovery against CoV diseases. |
