Researchers Worry COVID Will Quickly Develop Resistance To New Pills From Pfizer And Merck

If it wasn’t already bad enough that several experts have warned that US regulators are overlooking safety risks associated with the new generation of COVID therapeutic pills from Pfizer and Merck, researchers and regulators are also apparently worried that they might not even work – at least, not for long.

According to a report in WSJ, researchers and academics are already taking steps to keep an eye out for signs that COVID is evolving in response to exposure to pills like Paxlovid and Molnupiravir.

The hope is that the pills will save more lives, especially now that the vaccines and boosters have been surprisingly ineffective at prevent transmission and infection with the virus.

“We know this is likely to happen at some point, so we need to beat it to the punch and nip it in the bud before it gets out of hand and starts to take over,” said Katherine Seley-Radtke, a medicinal-chemistry professor at the University of Maryland, Baltimore County, whose lab is studying antiviral combination therapies.

The manufacturers of the pills say that the length of a course – which is taken over just five days, too short for the virus to develop immunity, they say. Then again, nobody knows for sure.

Some believe what we know about how other viruses react to drugs might offer some insights: for example, HIV is more likely to develop a resistance to treatments consisting of a single drug, hence the use of cocktails. But HIV is a chronic disease, not an acute infection like COVID.

For what it’s worth, researchers working for Pfizer and Merck say they saw no signs of resistance emerging during their clinical trials. But those only included a few hundred people. And there’s always the question of whether efficacy will fade when faced with new variants.

“As with any virus, SARS-CoV-2 being no exception, there is a potential for the emergence of resistance that can impact existing therapies,” the agency said. “As such, the FDA put mechanisms in place as part of the authorizations to help the agency understand the potential impact of variants on these products.”

Independent researchers cited by WSJ say they suspect Paxlovid might be more likely to cause resistance to develop. That’s because Paxlovid stops the virus by blocking an enzyme—called protease which is involved in replication.

Molnupiravir, on the other hand, is in a different class of antivirals. It stops the virus from multiplying by tricking an enzyme that SARS-CoV-2 needs to replicate into inserting errors into the genome of the coronavirus, short-circuiting the replication process and killing the virus.

Using a combination of drugs might help prevent resistance from developing. But as things stand, with these new drugs still in short supply, that might not be realistic.

Not to worry: Big Pharma is already looking at combining the new drugs with older (and less effective) treatments like remdesivir.

With so much research needed, researchers are preparing to conduct nearly 20 new trials seeking to enroll more than 100 participants each will be starting in the near future.