| RRC ID |
85437
|
| Author |
Nakagawa Y, Fujii M, Ito N, Ojika M, Akase D, Aida M, Kinoshita T, Sakurai Y, Yasuda J, Igarashi Y, Ito Y.
|
| Title |
Molecular basis of N-glycan recognition by pradimicin a and its potential as a SARS-CoV-2 entry inhibitor.
|
| Journal |
Bioorg Med Chem
|
| Abstract |
Virus entry inhibitors are emerging as an attractive class of therapeutics for the suppression of viral transmission. Naturally occurring pradimicin A (PRM-A) has received particular attention as the first-in-class entry inhibitor that targets N-glycans present on viral surface. Despite the uniqueness of its glycan-targeted antiviral activity, there is still limited knowledge regarding how PRM-A binds to viral N-glycans. Therefore, in this study, we performed binding analysis of PRM-A with synthetic oligosaccharides that reflect the structural motifs characteristic of viral N-glycans. Binding assays and molecular modeling collectively suggest that PRM-A preferentially binds to branched oligomannose motifs of N-glycans via simultaneous recognition of two mannose residues at the non-reducing ends. We also demonstrated, for the first time, that PRM-A can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vitro. Significantly, the anti-SARS-CoV-2 effect of PRM-A is attenuated in the presence of the synthetic branched oligomannose, suggesting that the inhibition of SARS-CoV-2 infection is due to the interaction of PRM-A with the branched oligomannose-containing N-glycans. These data provide essential information needed to understand the antiviral mechanism of PRM-A and suggest that PRM-A could serve as a candidate SARS-CoV-2 entry inhibitor targeting N-glycans.
|
| Volume |
105
|
| Pages |
117732
|
| Published |
2024-5-1
|
| DOI |
10.1016/j.bmc.2024.117732
|
| PII |
S0968-0896(24)00146-9
|
| PMID |
38643719
|
| MeSH |
Animals
Antiviral Agents* / chemical synthesis
Antiviral Agents* / chemistry
Antiviral Agents* / pharmacology
COVID-19 / virology
COVID-19 Drug Treatment
Chlorocebus aethiops
Humans
Polysaccharides* / chemistry
Polysaccharides* / pharmacology
Pradimicins and Benanomicins*
SARS-CoV-2* / drug effects
Vero Cells
Virus Internalization* / drug effects
|
| IF |
3.073
|
| Resource |
| Human pathogenic viruses |
SARS-CoV-2( JPN/NGS/SC-1/2020) |
