Molecular virologist fights influenza at the molecular level: A study of how experimental inhibitors bind a key flu protein may guide novel antiviral compounds

The two experimental inhibitors studied by Petit, a UAB assistant professor of biochemistry and molecular genetics, are small molecules whose precise mechanism of action was unknown. The inhibitors target the function of a key influenza protein called NS1, which has multiple roles to block the body’s immune response during influenza infection. Thus, NS1 is essential to the survival and adaptability of the influenza virus. Petit and colleagues used nuclear magnetic resonance, or NMR, spectroscopy to probe interactions of the inhibitors with NS1. They first showed that the inhibitors — called A9 and A22 — interacted with just one of the two independently folded domains of NS1, the NS1 effector domain. The researchers noted that the structures of both small-molecule inhibitors were very similar to a fragment of a host protein called CPSF30 that the NS1 effector domain binds in order to short-circuit the body’s immune response. Therefore, the researchers hypothesized that A9 and A22 block influenza viral replication and block NS1 function by interfering with the interaction between the NS1 effector domain and CPSF30.See it on Scoop.it, via Viruses, Immunology & Bioinformatics from Virology.uvic.ca
Molecular virologist fights influenza at the molecular level: A study of how experimental inhibitors bind a key flu protein may guide novel antiviral compounds
Source: Viral Bioinformatics