Publication date: Mar 22, 2025
Medical treatments using potent neutralizing SARS-CoV-2 antibodies have achieved remarkable improvements in clinical symptoms, changing the situation for the severity of COVID-19 patients. We previously reported an antibody, NT-108 with potent neutralizing activity. However, the structural and functional basis for the neutralizing activity of NT-108 has not yet been understood. Here, we demonstrated the therapeutic effects of NT-108 in a hamster model and its protective effects at low doses. Furthermore, we determined the cryo-EM structure of NT-108 in complex with SARS-CoV-2 spike. The single-chain Fv construction of NT-108 improved the cryo-EM maps because of the prevention of preferred orientations induced by Fab orientation. The footprints of NT-108 illuminated how escape mutations such as E484K evade from class 2 antibody recognition without ACE2 affinity attenuation. The functional and structural basis for the potent neutralizing activity of NT-108 provides insights into the rational design of therapeutic antibodies.
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Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | COVID-19 |
| drug | DRUGBANK | Sulfasalazine |
| pathway | KEGG | Viral replication |
| disease | IDO | host |
| drug | DRUGBANK | Serine |
| disease | IDO | protein |
| disease | MESH | Middle East Respiratory Syndrome |
| disease | IDO | role |
| disease | MESH | weight loss |
| disease | MESH | infection |
| drug | DRUGBANK | Proline |
| drug | DRUGBANK | Medical air |
| drug | DRUGBANK | Water |
| disease | MESH | Body weight change |
| disease | IDO | site |
| drug | DRUGBANK | Amino acids |
| drug | DRUGBANK | Sodium lauryl sulfate |
| drug | DRUGBANK | Nitrogen |