Aspirin (Acetylsalicylic Acid) Inhibits HCV Replication in Laboratory Study  Due
to the limitations of interferon-based therapy
for chronic hepatitis C virus (HCV) infection, researchers have explored various
alternative therapies. In the May 2008 issue of Hepatology, Mexican researchers
reported on a laboratory study of the anti-HCV activity of acetylsalicylic acid,
better known as aspirin.
The investigators were interested in testing
acetylsalicylic acid against HCV because it has previously been reported that
salicylates inhibit the replication of other flaviviruses including Japanese encephalitis
virus and dengue virus.
In the present study, the researchers examined
the effects of acetylsalicylic acid on viral replication and protein expression
using an HCV subgenomic replicon cell culture system. They incubated Huh7 replicon
cells with 2-8 mM acetylsalicylic acid for different durations, and measured HCV
RNA and protein levels using Northern blot, Western blot, and real-time polymerase
chain reaction (PCR) assays.
Results
•
Acetylsalicylic
acid had a suppressive effect on HCV RNA and protein levels of nearly 58%.
•
Acetylsalicylic
acid-dependent inhibition of HCV expression was not mediated by the 5'-internal
ribosome entry site or 3'-untranslated regions.
•
However, HCV-induced
cyclooxygenase 2 (COX-2) messenger RNA and protein levels and activity were down-regulated
by acetylsalicylic acid, possibly via a nuclear factor kappa-B (NF-kappa-B)-independent
mechanism.
•
Acetylsalicylic
acid-dependent inhibition of viral replication was due in part to inhibition of
COX-2 and activation of p38 and MEK1/2 mitogen-activated protein kinases (MAPKs).
•
Inhibition
of these kinases, for example by short interfering RNA silencing, blocked the
antiviral effect of acetylsalicylic acid.
The
investigators concluded that, "our findings suggest that the anti-HCV effect
of acetylsalicylic acid in the Huh7 replicon cells is due to its inhibitory effect
on COX-2 expression, which is mediated in part by the activation of MEK1/2/p38
MAPK."
These findings, they added, "suggest the possibility that
acetylsalicylic acid could be an excellent adjuvant in the treatment of chronic
HCV infection."
6/20/08 Reference
K
Trujillo-Murillo, AR Rincon-Sanchez, H Martinez-Rodriguez, and others. Acetylsalicylic
acid inhibits hepatitis C virus RNA and protein expression through cyclooxygenase
2 signaling pathways. Hepatology 47(5): 1462-1472. May 2008. |
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