Curing the flu

[Teleological]

An article from Sciencedaily:
Protein Structure Discovery Opens Door For Drugs To Fight Bird Flu, Other Influenza Epidemics

Researchers at Rutgers University and The University of Texas at Austin have reported a discovery that could help scientists develop drugs to fight the much-feared bird flu and other virulent strains of influenza.

The open-access scientific article is here:
Structural basis for suppression of a host antiviral response by influenza A virus

Influenza A viruses are responsible for seasonal epidemics and high
mortality pandemics. A major function of the viral NS1A protein, a
virulence factor, is the inhibition of the production of IFN-b mRNA and
other antiviral mRNAs. The NS1A protein of the human influenza
A/Udorn/72 (Ud) virus inhibits the production of these antiviral mRNAs
by binding the cellular 30-kDa subunit of the cleavage and polyadenylation
specificity factor (CPSF30), which is required for the 3' end processing
of all cellular pre-mRNAs. Here we report the 1.95-Å resolution
X-ray crystal structure of the complex formed between the second and
third zinc finger domain (F2F3) of CPSF30 and the C-terminal domain of
the Ud NS1A protein. The complex is a tetramer, in which each of two
F2F3 molecules wraps around two NS1A effector domains that interact
with each other head-to-head. This structure identifies a CPSF30 binding
pocket on NS1A comprised of amino acid residues that are highly
conservedamonghumaninfluenzaAviruses. Single amino acid changes
within this binding pocket eliminate CPSF30 binding, and a recombinant
Ud virus expressing an NS1A protein with such a substitution is attenuated
and does not inhibit IFN-b pre-mRNA processing. This binding
pocket is a potential target for antiviral drug development. The crystal
structure also reveals that two amino acids outside of this pocket, F103
and M106, which are highly conserved (>99%) among influenza A
viruses isolated from humans, participate in key hydrophobic interactions
with F2F3 that stabilize the complex.

Basically, the NS1A protein is a virulence factor that is conserved in the vast majority of influenza viruses. It binds to and inhibits the activity of the CSF30 protein, which in turn is needed for RNA-processing of various proteins involved in the immune response, including IFN-b . The solved protein-structure allows researcher to design drugs that specifically inhibit this NS1A protein (Figure 1).

Figure 1: Mechanism of action and drug target.​

The structure of the protein can be found here:
Protein Data Bank: 2rhk.pdb

Perhaps the Linux-savvy guys with access to big CPUs (supercooled, modded, multi-core etc) can help in discovering a drug. Or anyone else for that matter.

Ubuntu 8.04 and Autodock 4 are all that is needed.

Maybe a MyBB competition to see who can get the best compound? Interested?

 

[Picard]

Perhaps the Linux-savvy guys with access to big CPUs (supercooled, modded, multi-core etc) can help in discovering a drug. Or anyone else for that matter.

Maybe a MyBB competition to see who can get the best compound? Interested?

Uhm, yeah. I agree, although that IFN-b protein doesn't look very 'lekker' to me.

 

[Teleological]

Uhm, yeah. I agree, although that IFN-b protein doesn't look very 'lekker' to me.

Not sure what you mean, but is it fixed now?

Anybody interested in making good use of all their extra CPU power?

 

[Picard]

Not sure what you mean, but is it fixed now?

I'm also not sure what I meant.

Closest I've come to this field is my best friend's descriptions about the protein secretion of yeast cells on which he's doing research for his Ph.D in Belgium. That and matric Biology.