Use of salicylate in treatment of SARS - possible contraindication ( Aspirin makes SARS worse)

Promedmail ^ | April 27, 2003 | David E Pulleyblank, Professor of Biochemistry

[TaxRelief]

(This is a very technical article: See translation in comment, below.)

Assuming that, as in the case of mouse hepatitis coronavirus (MHV), activation of p38 MAP-kinase contributes to SARS virus replication, these results suggest that salicylates (aspirin) should NOT be given to SARS patients. In view of the antipyretic effects of ASA (acetylsalicylic acid, aspirin) this drug is likely to be in widespread use among early-stage SARS patients. It could be a factor contributing to the severity of the syndrome. For this reason I believe it imperative that ASA use among SARS patients be assessed as rapidly as possible in order to determine whether it has contributed to the severity of individual cases.

It gets more complicated, but interesting:

In a follow-up to my earlier posting [see part 1 above] concerning the possible utility of p38 MAP-kinase inhibitors in the treatment of SARS, I have located a number of references where p38 MAP-kinase has been reported to be ACTIVATED by salicylates.

Two publications have described the effect of the p38 MAP-kinase (mitogen-activated protein kinase) inhibitor SB203580 on mouse hepatitis virus strain 3 (MHV)(McGilvray ID, et al. J Biol Chem 1998; 273(48): 32222-9 and Banerjee S, et al. J Virol 2002; 76(12): 5937-48). In the latter paper the authors state that MHV activation of the p38 MAP-kinase pathway results in phosphorylation of the translation initiation factor eIF4E, which in turn contributes to a high level production of virus. SB203580 reduced MHV particle production by a factor of 3.

Although there is as yet no direct evidence to suggest that the SARS coronavirus uses the p38 MAP-kinase pathway, phosphorylation of eIF4E is likely to prove a conserved coronaviral mechanism for directing cellular protein synthesis towards production of viral particles. SB203580 also has potent anti-inflammatory activity: (see: Ermert M, et al. Cyclooxygenase-2-dependent and thromboxane-dependent vascular and bronchial responses are regulated via p38 mitogen-activated protein kinase in control and endotoxin-primed rat lungs. Lab Invest 2003; 83(3): 333-47).

These findings suggest p38 MAP-kinase may prove a useful target for the control of SARS symptoms and possibly also to limit replication of the virus. Perhaps p38 MAP-kinase inhibitors could have application in in the treatment of SARS? I gather that 3 such compounds (SB281832, BiRB0797, and Ro320-1195) have gone through phase II clinical trials for treatment of asthma and/or rheumatoid arthritis and that pharmacokinetics and potential toxicities of these compounds must therefore have been characterized.

[riri]

I thought aspirin impeded the reproduction of viruses

I have always thought a fever reducer of any kind allowed a virus to multiply and prolonged illness. I always try and let the fever "do it's job".

[riri]

A temp over 104 is a different story

That was always my belief,too. In fact my husnband and I differ on this. And he has agreed to let me allow the kids to run the fever UNLESS it gets to 104.

Not to mention, a fever masks symtoms and allows people to go out and about spreading the virus along.

[vetvetdoug]

Viruses are in many cases, temperature sensitive. A fever will cause the virus to decrease replication and therefore decrease the severity of the disease. Prostaglandins may also be decreased which may be involved in the loss of inhibition of the viral replication. This on the molecular level will need further investigation with the specific SARS virus which will give a lot of molecular biologists and virologists some real fodder for phD's and Masters theses.

[bonesmccoy]

If the disease has a hemorrhagic component to it's clinical presentation (like Hantaan virus); ASA should be contraindicated for symptomatic relief.

From the context of the ProMed discussion, p38 activation plays a role in viral replication through an intermediary which up-regulates transcription.

p38 appears to play a role in the process used by the virus to hijack the cellular processes.

These processes are converted and applied to the transcription of viral proteins, permitting assembly of viral particles.

This all reminds one of Democrat/socialist politic.

The GOP/conservatives actually invest cash, build a company, and provide a service. The DNC then inserts an operative into the GOP company. This virus then spreads through the surrounding community by hijacking the one company's operations and cloning new DNC-like operatives.

(only half-kidding)

[Domestic Church]

It has been demonstrated in the past that use of aspirin for the common cold increases the amount of virus in exudate...of course this raised the possibilty that the study which was referenced in the media some years ago, might have had backing from the aspirin industry. The important thing is that aspirin is still a common treatment for colds/flu and many people are on long term apirin therapy for chronic illness and if indeed it increases the infectious rate of SARS it has to be addressed.