What Are the COVID-19 Antiviral Pills?

When you get sick, there are many treatment options to help you get better. For a bacterial infection, doctors might prescribe antibiotics. A seasonal respiratory virus, like a common cold or flu, might be treated with fluids, rest and over-the-counter medicine geared to treat your symptoms.

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For people diagnosed with serious conditions such as COVID-19, which is caused by the SARS-COV-2 virus, other kinds of medication might be helpful. Common treatments prescribed to date include monoclonal antibodies and convalescent plasma.

"The rationale for these treatments is we're using antibodies that will combine with parts of virus cells," says critical care physician Abhijit Duggal, MD. "By attaching themselves to the cell, and impacting the shape of the cell, these antibodies are going to minimize the virus's ability to go and cause problems."

Over the years, however, doctors have started developing antiviral medications to treat certain conditions. For example, on December 22, 2021, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for a pill developed by Pfizer to treat mild-to-moderate COVID-19. These antivirals differ from antibody-related treatments in significant ways.

What are antiviral pills?

A virus consists of genetic material surrounded by a capsid, or a protective covering made of proteins. To reproduce, viruses worm their way into your body's cells, and then use this space as an incubator to produce more copies of themselves. However, if this process is interrupted or disrupted at some point along the way, the virus will stop replicating.

That's the goal of antiviral pills. They go right to the source — the virus cells — and interrupt their usual activities. "Antiviral pills act directly on the virus itself, and either disrupt the reproduction cycle of the virus — meaning the virus can't replicate — or cause direct damage to the virus, where you're decreasing how effective it is," Dr. Duggal says.

Antiviral pills are already used to treat HIV, hepatitis B and hepatitis C. Tamiflu, which you may have taken after catching the flu, is also an antiviral. More recently, an antiviral medication called remdesivir was initially used to treat COVID-19.

How do antiviral pills work?

Your body is made up of many building blocks, including proteins called enzymes. An enzyme known as protease is tasked with breaking down other proteins, such as the ones used to help viruses replicate.

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Antiviral pills contain protease inhibitors. To put it simply, these protease inhibitors disable the specific protease enzyme (or protein) that enables a virus to function normally — that is, to reproduce — in your body. "Protease inhibitors have been used in medications to treat other viral illnesses for a while," says Dr. Duggal. "Protease inhibitors act on the virus's specific protein development aspects."

Not all antiviral pills are one-size-fits-all medications, however. "The problem is, you need to figure out which chemical is going to disrupt the protein associated with the specific virus itself," says Dr. Duggal. For example, drugs used to treat HIV are calibrated specifically for those virus proteins.

Where the COVID-19 pills are concerned, Pfizer developed theirs specifically to work against a protease called 3CL, which is associated with SARS-COV-2. "This medication disrupts the development of that protease," says Dr. Duggal. "By doing that, the virus cell isn't going to be able to sustain itself. When its replication stops, you basically drop the overall number of cells."

Many antiviral medications combine multiple protease inhibitors. For example, the Pfizer COVID-19 pill puts together two: ritonavir, which has been used to fight viral illnesses such as HIV and hepatitis B; and a new protease inhibitor, nirmatrelvir, developed by Pfizer. Working together, these protease inhibitors appear to help decrease the overall viral burden in your body.

Who should take the COVID-19 antiviral pills?

Even though these antiviral pills have been approved for emergency use by the FDA as a COVID-19 treatment, they aren't for everyone. According to the FDA, the prescription-only pills are "for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults and pediatric patients (12 years of age and older weighing at least 40 kilograms or about 88 pounds) with positive results of direct SARS-CoV-2 testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death."

In other words, you won't be using them to prevent yourself from catching the virus. "The way to think about these medications is it seems that if you have been exposed and are now potentially developing the disease, or are at a higher risk of developing the disease because of exposure to the virus, they decrease your risk pretty significantly," says Dr. Duggal.

"Think of these as like a post-exposure medication that you're taking to make sure that you don't develop viral titers (concentration levels) high enough that might cause you to have a bad infection, or severe disease. Your primary prevention still would be if you were vaccinated because your risk is going to definitely be much, much lower than anything else."

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The reason you just don't want to start taking COVID-19 pills "just in case" you might get sick is that viruses can become drug-resistant. "Resistance against medications is always a problem," says Dr. Duggal. "Even in other diseases, when you're using antivirals, you want to be very mindful of how you use them so you don't develop resistance against those medications. You want to save these medications for people who really need them. If people do just start taking pills in hopes it'll decrease their risk, the risk of the virus developing resistance against this pill is going to go up very, very quickly. And the risk of this becoming ineffective would be a huge problem for us at that time."

Virus mutations are also always a constant presence as new medications are being developed. "Viruses are smart," says Dr. Duggal. "Viruses are actively mutating. They change their structure in specific ways where things that we're using to impact them goes down."

If a new variant comes that now has a mutation, it's possible that these medications either won't be as effective or may not work at all, Dr. Duggal notes. This is what we're seeing with SARS, and it's not out of the ordinary. "With most respiratory viral illnesses, the risk of mutation is much higher than other viruses," says Dr. Duggal."That's why it becomes a lot trickier to handle. And it's such an actively evolving situation with such a high disease burden, so the risk of mutations is always going to be higher."

Dr. Duggal adds that because the COVID-19 pills now approved for emergency use are based on protease inhibitors, these medications should be in a better place to handle virus mutations. "When we talk about these protease inhibitors disrupting something, and it just stops working — that's good," he says. "It's difficult for the virus to mutate very quickly at the cellular level. It's possible, but obviously going to be much more complex." However, Dr. Duggal stresses once again that these pills should still be reserved for people who really need them. "The virus has a higher chance of developing resistance the more you expose the virus to these pills."

Getting vaccinated is important

Antiviral pills to treat COVID-19 are not a substitute for vaccination.

At the moment, getting vaccinated is the most crucial step you can take, as trying to disrupt the overall cycle of virus replication through herd immunity is the best way to bring the pandemic under control. Along with that, Dr. Duggal recommends tried-and-true methods to keep the virus at bay, such as masking, social distancing and washing your hands.

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