tetano
Editor, Senior Moderator
PLoS One. 2014 Apr 9;9(4):e94392. doi: 10.1371/journal.pone.0094392. eCollection 2014.
The mechanism of poly-galloyl-glucoses preventing influenza a virus entry into host cells.
Ge H1, Liu G2, Xiang YF3, Wang Y1, Guo CW2, Chen NH1, Zhang YJ4, Wang YF5, Kitazato K2, Xu J1.
Author information
Abstract
Hemagglutinin (HA) is essential for Influenza A virus infection, but its diversity of subtypes presents an obstacle to developing broad-spectrum HA inhibitors. In this study, we investigated the molecular mechanisms by which poly-galloyl glucose (pGG) analogs inhibit influenza hemagglutinin (HA) in vitro and in silico. We found that (1) star-shaped pGG analogs exhibit HA-inhibition activity by interacting with the conserved structural elements of the receptor binding domain (RBD); (2) HA inhibition depends on the number of galloyl substituents in a pGG analog; the best number is four; and when PGG binds with two HA trimers at their conserved receptor binding domains (loop 130, loop 220, and 190-α-helix), PGG acts as a molecular glue by aggregating viral particles so as to prevent viral entry into host cells (this was revealed via an in silico simulation on the binding of penta-galloyl-glucose (PGG) with HA). pGGs are also effective on a broad-spectrum influenza A subtypes (including H1, H3, H5, H7); this suggests that pGG analogs can be applied to most influenza A subtypes as a prophylactic against influenza viral infections.
PMID:
24718639
[PubMed - in process]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/24718639
The mechanism of poly-galloyl-glucoses preventing influenza a virus entry into host cells.
Ge H1, Liu G2, Xiang YF3, Wang Y1, Guo CW2, Chen NH1, Zhang YJ4, Wang YF5, Kitazato K2, Xu J1.
Author information
Abstract
Hemagglutinin (HA) is essential for Influenza A virus infection, but its diversity of subtypes presents an obstacle to developing broad-spectrum HA inhibitors. In this study, we investigated the molecular mechanisms by which poly-galloyl glucose (pGG) analogs inhibit influenza hemagglutinin (HA) in vitro and in silico. We found that (1) star-shaped pGG analogs exhibit HA-inhibition activity by interacting with the conserved structural elements of the receptor binding domain (RBD); (2) HA inhibition depends on the number of galloyl substituents in a pGG analog; the best number is four; and when PGG binds with two HA trimers at their conserved receptor binding domains (loop 130, loop 220, and 190-α-helix), PGG acts as a molecular glue by aggregating viral particles so as to prevent viral entry into host cells (this was revealed via an in silico simulation on the binding of penta-galloyl-glucose (PGG) with HA). pGGs are also effective on a broad-spectrum influenza A subtypes (including H1, H3, H5, H7); this suggests that pGG analogs can be applied to most influenza A subtypes as a prophylactic against influenza viral infections.
PMID:
24718639
[PubMed - in process]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/24718639