How do the new COVID-19 antiviral pills work?

Drugmakers Pfizer and Merck have both submitted COVID-19 antiviral pills to the FDA for approval.

Pfizer says its pill Paxlovid cut rates of hospitalization and death by nearly 90 per cent and Merck’s pill Molnupiravir claims a reduction by 50 per cent.

Both drugs work by focusing on disrupting the virus directly.

Dr. Alon Vaisman, infectious disease and infection control physician with the University Health Network explains that they both use well-established mechanisms and science, but treating respiratory viruses with such medications is a new innovation.

Merck: Molnupiravir

Dr. Vaisman says Merck’s Molnupiravir pill was originally intended to fight influenza but was never fully established as a drug to fight that virus. It has now been revived and repurposed for COVID-19.

He explains that the medication is a nucleoside analogue that interferes with the virus’ replication in the body.

“Imagine that [the virus’] RNA is made out of building blocks. It uses these building blocks to develop its genetic code,” Dr. Vaisman explains. “[Molnupiravir] is an analogue of the genetic sequence or one genetic part of the virus.”

An “analogue” can be better understood as a fake building block. When the virus uses it in its replication process, and it is “integrated into the virus genome,” the replication malfunctions, mutations happen and the virus is killed off.

“So this nucleoside analogue essentially acts like a building block that takes the place of what should have normally been there, but causes the replication to fail,” said. Dr. Vaisman.

He adds that other drugs used to treat herpes, HIV or Hepatitis B are also nucleoside analogues and act in a similar fashion.

Fun fact: If Molnupiravir sounds familiar, Dr. Vaisman says that’s because it was named after Mjolnir, Norse god Thor’s hammer.

Pfizer: Paxlovid

Pfizer’s drug Paxlovid is in the class of medications called protease inhibitors.

“The way a protease inhibitor works is by inhibiting a protein that’s involved in the replication of the genome,” explains Dr. Vaisman.

The drug interrupts the viral life cycle and stops the virus from multiplying by blocking a “protease” or an essential enzyme, that the virus needs in order to replicate.

“Protease inhibitors are medications that we use for Hepatitis C and HIV. [Paxlovid] is using a mechanism that is already well established in other medications,” said. Dr. Vaisman.

When these medications may be used

Dr. Vaisman says antivirals can be used to treat a disease prior to getting it, in the early stages or when it is a severe illness and the patient needs to be hospitalized.

The Pfizer and Merck pills cannot be used as pre-exposure prophylaxis (PREP) like some other medications, he explains, as they will not prevent you from getting COVID-19. Merck’s pill was also shown to be ineffective when used on people already admitted to hospital with COVID-19, he adds.

“So many drugs have been tried for various indications, like COVID-19, in all three of these phases. We’ve settled on a few that work for different phases,” said Vaisman. “This one is really just for that middle phase when you’re not hospitalized, but you have the disease.”

The idea is to prevent those who have been infected with the virus from getting even sicker and being hospitalized.

“The reason that’s important is because with COVID in particular, what we see is that the people don’t get admitted to hospital on day one or day two. It’s often a little bit later,” said. Dr. Vaisman. “So if you’re able to intervene early, then you’re able to prevent the bad outcomes.”

Impacts on the body

There is not much clinical data available yet in terms of side effects for either pill. However, Dr. Vaisman says we can look to other drugs in the same class as examples of how they work inside the body.

Some antiviral medications can have toxicity for the kidney, liver or other parts of the body.

“It remains to be seen how toxic these medications will be in the long run for people. But if it’s similar to the other medications in its class, it’s generally well-tolerated” and is anticipated to be a short course of treatment, he said.

Immune system

Neither of the pills has any bearing on the immune system.

“The overall effect of the drug is not directly onto your immune system, so it’s not thought to be boosting your immune system in that way or blocking any part of your immune system,” said. Dr. Vaisman. “The primary mechanism of action is directly on the virus itself.”

Fertility

Dr. Vaisman says neither nucleoside analogue (Merck) or protease inhibitors (Pfizer) are known to have any effects on fertility.

“If it’s similar to the current medications, the same classes, there isn’t an effect on fertility in those medications,” he confirmed.

DNA

Neither of the medications affects human DNA.

“There isn’t concern that this will integrate into your DNA and cause any kind of genetic issues — cancer or anything like that,” said Dr. Vaisman.

He adds that like other antiviral medications, the new pills meant to fight COVID-19 will likely result in some side effects, but none related to DNA.

Prevention is better than cure

Despite the great strides being made in the development of antivirals against COVID-19, Dr. Vaisman says vaccines are still the best protection against the virus and antivirals should be seen as a secondary line of defence.

“No pill is ever going to be as effective at preventing severe illness as a vaccine,” he said. “This idea of not trusting vaccine versus trusting medication … you’re exposing yourself to potential side effects [from medication] too. If we think about the COVID vaccine, it’s has a very favourable side effect profile compared to medications and even compared to other vaccinations.”