ANTIVIRALS POTENTIATED BY THE INHIBITORS OF INOSINE 5 ́- MONOPHOSPHATE DEHYDROGENASE

Remy

Administrator
IMP dehydrogenase inhibitors seem to work by preventing the degradation of inosine to xanthosine.

From Wikipedia:

IMP dehydrogenase EC 1.1.1.205 (Inosine-5'-monophosphate dehydrogenase) (Inosinic acid dehydrogenaseis) (IMPDH) an enzyme that converts inosine monophosphate to xanthosine monophosphate:[2][3][4][5]
This is interesting given that many of us have tried taking additional inosine to boost immunity. This seems like another way to increase inosine levels.

This study shows that taking an antiviral such as acyclovir along with an IMP dehydrogenase inhibitor significantly increased the effectiveness of the antiviral.

@Strike me lucky, they've used this combo with zoster as well.

Full text here.

The inhibitory effect of ACV on herpes- virus replication could be changed by a combination with drugs, inhibitors of key enzymes from the cell methabolism. Marked enhancement of the antiviral acti- vity of ACV was achieved after combina- tion with inhibitors of IMP dehydrogenase (Figure).

IMP dehydrogenase / IMPDH; EC 1.1.1.205 / is the rate-limiting enzyme in the the novo pathways of the purine metha- bolism. The enzyme catalyzes NAD-de- pending conversion of Inosine monophos- phate (IMP) to Xantosine monophosphate (XMP). In cells infected with herpesvirus the concentration of the dGTP is reduced as result of IMP dehydrogenase inhibition and the possibility of triphosphate form of ACV to interact with viral DNA po- lymerase is increased. Wherever, signifi- cant inhibition of the herpesvirus replica- tion is achieved.

It has been demonstrated that Rbv, MPA and MZR markedly enhanced the antiherpes activity of ACV .

Ribavirin
Ribavirin (1-β-D-ribofuranisyl-1, 2, 4-tria- zole-3-carboxamide) is a synthetic nucleo- side structuraly related to pyrazofurin (pyrazomycin), guanosine and xanthosine. The drug has been known as antiviral agent and also has moderate antitumor and im- munossupressive effects /9/.

Rbv has activity against many RNA vi- ruses, including respiratory sincitial virus, influenza A and B viruses, parainfluenza virus and rhinovirus /10, 11/. Oral Rbv was used in combination with interferon-α for treatment of chronic hepatitis C infection in patients with compensated liver disease /12/. Rbv has been effective for therapy of pneumonitis caused by adenoviruses /13/.

Rbv acts also on replication of DNA vi- ruses, like Poxviruses, alone or in combi- nation with Cidofovir /14/.
The inhibitory activity of Rbv on viral replication depends on the intracellular conversion to Rbv-5 ́-monophosphate, - diphosphate and triphosphate. Rbv-5 ́- triphosphate functions as inhibitor of viral RNA polymerase. Rbv-5 ́-monophosphate acts on viral RNA and DNA synthesis through prevention of the formation of guanisine monophosphate, respectively GTP , after IMP dehydrogenase inhibition. In common, the specificity of action of Rbv is to a high degre depending on the kind of viral infection.

Rbv was found to be very effective on herpesvirus replication in combination with ACV / 15/. The potentiating effect of Rbv on inhibitory activity of ACV has been ex- amined in vitro and in vivo. It has been obtained about 63% inhibition of the virus yield in treatment of HSV-1 and PRV in cell cultures. The antiherpes effect of the combination has been restored after adding of Guanosine with ACV and Rbv /16/. The combination was applied successfully in the treatment of herpetic keratoconjunc- tivitis in rabbits /17/.
 

Get Our Free ME/CFS and FM Blog!



Forum Tips

Support Our Work

DO IT MONTHLY

HEALTH RISING IS NOT A 501 (c) 3 NON-PROFIT

Shopping on Amazon.com For HR

Latest Resources

Top