About five years ago, Pedersen contacted his Gilead contact, and the company sent him 25 or 30 molecules, drawn from the large library of drug candidates that pharmaceutical companies typically maintain. Two of the molecules worked wonderfully in cat cells infected with the FIP virus: GS-441524 and GS-5734, the latter of which is now better known as remdesivir.
Both GS-441524 and remdesivir work by blocking viral replication. These are nucleoside analogues, which means that they mimic the building blocks of nucleosides – A, U, C or G – that make up the genetic material of the virus. Specifically, they mimic “A”, and when the virus is prompted to incorporate a GS-441524 molecule or remdesivir instead of “A”, the replication process is stuck. Finally, no more letters can be added and the virus cannot replicate. Where the two drugs differ is that remdesivir has an additional phosphate group, a small change that helps it enter a cell and be used in replication. This modification is commonly used to improve the effectiveness of similar antivirals. “It was just one of those really smart things that worked perfectly,” said Katherine Seley-Radtke, an antiviral researcher at the University of Maryland in Baltimore County.
For some reason, however, this change did not make much difference in cat cells infected with the FIP virus. Both molecules were effective, so Pedersen decided to pursue the simpler one, GS-441524. He then infected 10 cats with PIF and administered GS-441524 to them. The 10 cats have recovered.
“We almost fell from our chairs,” says Weigner.It’s ridiculous, he remembers having thought. It can’t work as well. Wait, wait, stop, come back? What did he do? The initial study was small and under artificial conditions, but in a follow-up field trial of 31 pets with naturally acquired FIP, 25 eventually did – an unprecedented recovery rate. Pedersen had previously tested another Kansas State University antiviral, but only seven out of 20 cats were in remission. These results looked impressive at the time, but the GS-441524 looked even better.
Pedersen is now 76 years old and has dedicated 50 years of his career to FIP research. Finally, it seemed, a remedy was at hand. “I felt really good,” he told me, “and I thought it was a good cornerstone for my career.” But the cornerstone never materialized, at least not as he expected. Despite the success, Gilead refused to authorize GS-441524 for use in cats.
While Pedersen tested GS-441524 in cats, a different virus – a human virus – was rampant on the other side of the world in West Africa: Ebola. The virus that causes Ebola is not a coronavirus, but remdesivir has an unusually broad action for an antiviral, and the first results against Ebola were promising. So promising, in fact, that the company was considering FDA approval of remdesivir in humans.