Could oral antiviral pills be a game-changer for COVID-19? Infectious disease specialist explains why these options are absolutely necessary

The ability to treat COVID-19 with a pill rather than an injection or infusion means more people can be treated faster. (File photo: Hal Gatewood / Unsplash)

Almost two years after the start of the pandemic, it has become quite clear that we need better treatments for COVID-19 for people in the early stages of the disease.

Two new antiviral drugs may soon be the first effective oral treatments for COVID-19 to help keep people out of hospital. A Food and Drug Administration advisory committee plans to review the data supporting molnupiravir – a pill manufactured by Merck and its partner Ridgeback Therapeutics – on November 30, 2021.

And in early November, Pfizer released preliminary results from its antiviral pill, Paxlovid, another potentially promising tool for the treatment of COVID-19. On November 16, Pfizer formally requested authorization for emergency use of the oral pill from the FDA.

If these drugs are cleared in the coming weeks, they could be an important new treatment option for people with COVID-19, especially for those at high risk in the early stages of infection. The ability to treat COVID-19 with a pill rather than an injection or infusion means more people can be treated faster.

As an infectious disease physician and scientist at the University of Virginia, I have helped treat hundreds of people with COVID-19. I also helped run clinical trials to find new treatments. Molnupiravir and Paxlovid are said to fill a need that has not been met by other COVID-19 drugs, which are either difficult to administer or only suitable for hospital patients.

Here’s an overview of how important these new antiviral drugs are, how they work, and how they could be used.

Filling a gap in treatment

So far, researchers have found only a few effective drugs for treating COVID-19. Until now, only antiviral monoclonal antibodies could be used to treat out-of-hospital patients. However, these antibody-based drugs – which work by preventing the virus from entering cells – must be administered in a monitored environment such as a doctor’s office.

And many patients who could benefit from monoclonal antibodies do not have access to them because the administration sites are not located nearby. They are also not affordable for many people outside of the United States. In the United States, monoclonal antibodies are free for patients on emergency use clearance, but could ultimately become much more expensive if they receive full FDA approval.

Early data suggests that molnupiravir and Paxlovid are effective new drugs that patients can take at home to prevent complications from COVID-19 – which could be particularly beneficial for people at high risk of serious illness. Once approved, these pills will help treat patients earlier in the infection, when antiviral drugs are more effective. By preventing the virus from growing in the body early on, drugs can prevent the inflammation that causes severe COVID-19.

How molnupiravir and Paxlovid work

Molnupiravir works by causing the virus to record inaccurate genetic information. SARS-CoV-2 stores its instructions for making new viruses in an RNA strand. Inside the cell, the virus makes copies of the RNA and then continues to make duplicates of those copies. When a patient takes molnupiravir, the drug masquerades as one of the key molecules in RNA and gets incorporated into strands produced by the virus. When a strand of RNA containing molnupiravir is copied in turn, the virus makes errors in the copy. Over the course of several copying cycles, molnupiravir forces more and more errors until the virus is no longer able to function – a phenomenon in virology called “error catastrophe”.

Paxlovid uses a different mechanism to prevent the virus from replicating itself. SARS-CoV-2 creates proteins needed to build new viruses in the form of a long chain, called a polyprotein. But polyproteins have to be cut into smaller pieces by a viral enzyme called protease to become active. Paxlovid prevents the virus protease from doing this job, thus preventing the virus from completing its life cycle.

How COVID-19 Pills Would Be Used

There are currently two main forms of treatment for COVID-19 in the United States: antiviral and anti-inflammatory drugs. Antiviral drugs stop the virus from growing in the body and are given in the first few days after symptoms to prevent serious illness. Anti-inflammatory drugs moderate the immune response and are used to help sicker patients who need oxygen.

Molnupiravir and Paxlovid have been studied in separate clinical trials with similar designs. In both studies, the drugs were tested in ambulatory patients with risk factors for severe COVID-19 who were at an early stage of their illness. Both studies also looked at the likelihood of patients dying or being hospitalized. However, neither of the two studies has yet been peer reviewed.

Molnupiravir reduced the risk of death or hospitalization by approximately 50% in non-hospitalized adult patients with mild to moderate COVID-19 when treated within five days of symptom onset. Paxlovid reduced this risk by approximately 89% for patients treated within three days of symptoms and by 85% for patients treated within five days. It is important to note that no patient who took either drug died during the studies. Because the drugs haven’t been studied one-on-one, it’s hard to say whether one will be better than the other in the real world. In early November, Britain became the first country to approve the use of molnupiravir.

Molnupiravir has not helped hospital patients recover from COVID-19 faster. It is likely that Paxlovid would not be helpful at the time of hospitalization either. Most patients hospitalized with COVID-19 are sick because of unregulated inflammation, not because the virus is always replicating in their bodies.

If and when these drugs will be approved in the United States, they will likely be used for the same high-risk patients who are eligible for monoclonal antibodies today. However, monoclonal antibodies can still be used for pregnant people, people on dialysis, and some immunocompromised patients.

The United States has already purchased millions of doses of molnupiravir and Paxlovid in anticipation of their clearance. However, the pills will only be useful if people also have access to cheap, quick and accurate COVID-19 tests, which are currently scarce. If COVID-19 is diagnosed too late, patients will already be outside the window of time when antiviral drugs can help.

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Other antiviral drugs are in development, including an oral form of the first COVID-19 drug, remdesivir, and long-acting injectable monoclonal antibodies.

Researchers are also working to reuse existing drugs to treat COVID. Inhaled steroids like budesonide and an antidepressant called fluvoxamine show particular promise.

While it is exciting to see new treatments for COVID-19, prevention remains the best strategy. COVID-19 vaccines continue to be the most effective tool to help end the pandemic.

[Understand new developments in science, health and technology, each week. Subscribe to The Conversation’s science newsletter.]The conversation

Patrick Jackson, Assistant Professor of Infectious Diseases, University of Virginia

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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