New UCSD flu discovery could block illness entirely

Scientists led by a UC San Diego chemist reported progress recently in researching a universal flu drug, effective regardless of the strain.

Seth Cohen, a UCSD professor and co-founder of San Diego’s Forge Therapeutics, said the drug inhibits a critical viral enzyme by jamming molecular machinery common to all strains. It could reduce the flu’s severity or perhaps block it completely.

The drug blocks an enzyme containing the metal manganese. Such metalloenzymes form the basis of Forge’s technology, which is currently directed toward developing antibiotics, not antivirals.

“This enzyme is a component that allows the virus to steal the cellular machinery, so that the virus can reproduce using the human cells,” Cohen said. The drug interrupts this process by binding to the manganese ions.

While the results were only observed in lab testing of the viral enzyme, called RNA polymerase, further development in animal testing and eventually humans appears feasible, Cohen said.

UCSD retains the rights to the technology, so Forge or another company would need to license it to bring it to the market.

The results were presented at the 255th National Meeting & Exposition of the American Chemical Society in New Orleans. The drug is a modified version of another compound Forge developed.

The original compound bound to one of two manganese ions in the enzyme. The new version binds to both, making it much more effective, Cohen said.

Next, the effectiveness of the enzyme inhibitor needs to be tested against the entire virus, not just the enzyme. If the virus cannot mutate to bypass the drug, it should be effective therapeutically.

Another enzyme-inhibiting drug, baloxavir marboxil, is already on the market in Japan under the brand name Xofluza. It acts like Tamiflu, but can be taken once a day, compared to twice a day for Tamiflu.

Tamiflu works by a different mechanism, inhibiting a viral surface protein. So Xofluza and other RNA polymerase inhibitors represent a new approach to flu antivirals.

Cohen said the new compound appears to be more effective than Xofluza, although this must be established in human testing. That testing could take a couple of years to start if all goes well, he said.