Pfizer, Merck trial antiviral combos amid concerns over resistance to COVID-19 pills
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Pfizer (NYSE:PFE) and Merck (NYSE:MRK), the developers of the first oral medications for COVID-19 in the U.S., are advancing combination studies for their antiviral therapies as experts flag the risk of viral resistance to the newly authorized pills, The Wall Street Journal reports. 

Last month, the FDA greenlighted Paxlovid from Pfizer (PFE) and molnupiravir from Merck (MRK)/ Ridgeback Biotherapeutics as the first oral COVID-19 therapies for at-home use.

However, the mutations that allow viruses to evade the antivirals are a real danger for drugs like Paxlovid and molnupiravir, which are given alone for patients, unlike the combination regimens used in infections, such as HIV and hepatitis C.
âWe 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,â quoted Katherine Seley-Radtke, a medicinal-chemistry professor at the University of Maryland, Baltimore County. Her lab is trialing antiviral combination therapies.
The researchers from Pfizer (PFE) and Merck (MRK) have rebuffed such fears noting that they did not see drug resistance during their trials for the pills. Meanwhile, researchers and drugmakers said that the risk of drug resistance was low for Paxlovid and molnupiravir as the treatments are taken only for a shorter duration.
However, according to independent experts, the risk of resistance is higher for Paxlovid than molnupiravir due to their different mechanisms of action. While Paxlovid inhibits an enzyme called protease involved in viral replication, molnupiravir works by introducing errors into the genetic code of the virus. Molnupiravirâs structure, resembling genetic molecules, makes it harder for the virus to evade its effect, Dr. Seley-Radtke noted.
âSo far, weâre not seeing anything that concerns us, but weâre carrying on looking to see, you know, whether or not there is an Achillesâ heel within the strategy that we have,â said Annaliesa Anderson, Pfizerâs (PFE) lead researcher behind the development of Paxlovid. The company is developing new COVID-19 antivirals and evaluating what combination will be most effective out of several drug options, Dr. Anderson said. Last year, a peer-reviewed study indicated the efficacy of a Paxlovid infusion in combination with remdesivir from Gilead (NASDAQ:GILD). 
Meanwhile, Daria Hazuda, Merckâs (MRK) vice president of infectious-disease discovery, said that the company is looking at the potential of combining molnupiravir with other drugs, including remdesivir. Noting that the mutations linked to remdesivir are susceptible to molnupiravir, a combination regimen involving the two drugs could be attractive, Dr. Hazuda noted.
Read: On Friday, the FDA expanded the regulatory clearance for remdesivir allowing its use in non-hospitalized patients.