As you know Oseltamivir and Zanamivir are sialidase enzymes, breaking sialic acid from nuraminidase and releasing of flu virus. but when an entering virus coming to infect a cell must attach to sialic acid, then is it possible to inhibit the attachment?
Dear Javanmard
As you know mentioned protein (nuraminidase) is produced during viral life cycle in minimum scale and is used around the infected cell or cells. But theoretically it possible that enzyme destroyed receptors on other non infected cells and inhibit viral attachment.
During replication the influenza virus attaches to the interior cell surface using hemagglutinin that binds to sialic acid groups. However when the progeny viruses are released from the cell, neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins. Since the cleavage of the sialic groups is an integral part of influenza replication, neuraminidase inhibitors block the function of neuraminidase thereby blocking the release of virus, but not much effect on entry/cell attachment.
Yes, it is possible to inhibit attachment - by sialic acid mimics (that act as decoy receptors) or by sialic-acid binding proteins (that compete with the virus for attachment). The latter strategy is described in PMID: 24733924. Re decoys, I recall hearing that Neu5Ac2en, the sugar molecule that prompted the development of zanamivir etc was originally tested as an HA decoy. There's evidence that such things are part of our intrinsic defences against flu too (e.g. http://vir.sgmjournals.org/content/75/7/1769.long).
Paul
- Badges
- Science topic