Study discovers anti-viral potential in existing drugs

A new study by University molecular biology professor Thomas Shenk suggests that painkillers similar to aspirin are capable of inhibiting the reproduction of the human cytomegalovirus.

HCMV is a member of the herpes family, and although it generally does not induce syptoms in a normal, healthy adult, it may in people with compromised immune systems. It can also cause birth defects in infants.

"For people who are immunocompromised, such as people with AIDS or people who are transplant recipients, this virus is a big problem," Shenk said.

In the study, the research team drastically reduced the replication of the virus, by a factor of more than 100, by treating cultured cells in the laboratory with indomethacin.

Indomethacin, an over-the-counter drug that goes by the brand name Indocin, is "related to aspirin, but is a different compound that at high dosages inhibits HCMV," Shenk said.

Both aspirin and indomethacin are inhibitors of COX-2, an enzyme that is responsible for producing prostaglandin E2. Shenk and other researchers had noticed that an HCMV infection caused PGE2 levels to skyrocket, suggesting a connection between viral infection and PGE2.

The research team spent roughly two years investigating the nature of their relationship."When COX-2 is blocked, it then quite substantially blocks the growth of HCMV," Shenk said, explaining the team's results. "What we proved is that PGE2 is what's essential for the virus to reproduce."

Nonetheless, Shenk has addressed whether individuals can block HCMV themselves by taking large amounts of aspirin or indomethacin.

"I really don't know [if that would be possible]; we used very high concentrations of the drug, much greater than can be created in the human body," Shenk said. "But it hasn't been examined — it could be beneficial."

The current treatment for HCMV is ganciclovir, a drug that is very effective but also highly toxic. Because of its toxicity, it can only be administered in doses that are too small to be fully effective.

Because PGE2 inhibiting painkillers are better tolerated by the body than ganciclovir, Shenk expressed hope that using the two together will eventually prove to be a more effective treatment.

"We're interested in exploring a normal inhibitor that we can combine with ganciclovir to be more effective," Shenk said. "That's the next thing to start exploring."

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At this time, Shenk and his team do not know whether or not this method of inhibition might be effective for other families of viruses.

Deborah Yu '98, whom Shenk advised for her senior thesis, was a contributing author to the study. Parts of her thesis research were included in the study.

The report was released in last Tuesday's early edition of "The Proceedings of the National Academy of Sciences."