fredag 10. oktober 2014

Therapeutic HIV vaccine - RNA viruses - Ebola


Enzymatic cleavage of viral genomes: hydrolysis interchangeable with ammonolysis in a kind of nitrogen fixation.

This could also be relevant for Ebola, which also is a single-stranded RNA virus:

Therapeutic HIV vaccine

The body's initial "vaccine-reaction" against HIV could be prolonged if the viruses were inactivated. In comparison, the poliovirus can be inactivated by cleavage of its RNA by ammonia. Hopefully, the same can be true for HIV. Both viruses contain single-stranded RNA and hydrolytic proteases. Perhaps the proteases perform (catalyse) ammonolysis of the phosphodiester bonds in RNA, and so cut the strands. HIV has even RNase H which is specialized in breaking RNA strands. I guess there are proteins with nuclease activity also in the Ebola viruses, e.g. the nucleoprotein (NP). Maybe even coiled, viral RNA can work on itself as an ammonolytic ribozyme. The phosphorus/phosphate (PO4-) in RNA repels water more than it repels ammonia, and is thus favoring ammonolysis over hydrolysis. (NH3 is a stronger nucleophile and a slightly lighter molecule than H2O).
The tight encapsulation/packing of RNA in the viruses will promote the ammonolysis process. It brings the 2' hydroxyl group close to the phosphorus, catalysing breakage of the phosphodiester bonds. There is high inward osmotic pressure in viruses. The hydrophobic cores in the ribonucleoproteins will attract ammonia.
(The Ebola viruses are extra prone to breakage during mechanical stress in vivo because of their long, rod-shaped forms).
And the host cells use RNases to hydrolyse foreign RNA. Maybe the RNases switch to ammonolysis when ammonia is available, and thereby speed up this defense.
In this regard, inhalation of ammonia could be a way to destroy HIV and other RNA viruses in blood and tissue.

Written by:

Ottar Stensvold

Molde 
Norway

Principle of hydrolysis: