Publication date: Sep 03, 2025
DMBT1 is a large scavenger receptor cysteine rich (SRCR) B protein that has been reported as a tumor suppressor gene and a co-receptor for HIV-1 infection. Here we found DMBT1 is a major mucosal protein bound to SARS-CoV-2. Overexpression of DMBT1 in 293T cells may enhanced infection by SARS-CoV-2 in ACE2 dependent manner. Blocking experiments using overlapping peptide library of SRCR domain of DMBT1 showed that peptide 7 (CQGRVEVLYRGSWGTV), which contains bacteria-binding VEVLXXXXW motif, could inhibit SARS-CoV-2 infection. High concentration of peptide 7 can significantly inhibit the replication of SARS-CoV-2 in hamsters. Peptide 7 inhibits SARS-CoV-2 infection by aggregating the spike protein, thereby reducing its binding to and internalization by host cells. The cysteine residue at the N-terminus of peptide 7 is critical for dimerization and antiviral activity. These results indicate that DMBT1 can serve as a candidate target for the development of antiviral drugs.
| Concepts | Keywords |
|---|---|
| Cqgrvevlyrgswgtv | Antivirals |
| Hiv | DMBT1 |
| Rich | Mucosal innate immunity |
| Scavenger | SARS-CoV-2 |
| Tumor | SRCR domain |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | SARS-CoV-2 infection |
| pathway | REACTOME | SARS-CoV-2 Infection |
| drug | DRUGBANK | L-Cysteine |
| disease | IDO | protein |
| disease | MESH | infection |
| disease | IDO | bacteria |
| disease | IDO | replication |
| disease | IDO | host |