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Antiviral drug shows promise against COVID-19 and RSV

Scientists are working to develop antiviral compounds that could be effective against a range of different kinds of viruses. CROCOTHERY / Shutterstock

Vaccines against SARS-CoV-2, the virus that causes COVID-19, have saved hundreds of thousands of lives in the U.S. alone. But treatment options for COVID-19 are limited. One antiviral drug has been approved by the FDA to date, remdesivir. It can shorten recovery time for patients hospitalized with COVID-19. However, remdesivir needs to be given intravenously and has limited use. Other antiviral drugs are in development, including one called molnupiravir, which can be taken orally and is currently under review by the FDA for emergency use authorization.

Other antiviral drugs to treat COVID-19, especially ones available as pills to take at home, are urgently needed. The development of antivirals that could also be used to treat other serious respiratory infections, such as respiratory syncytial virus (RSV), is a priority as well. RSV infections hospitalize almost a quarter of a million young children and older adults every year in the U.S. There are currently no effective drugs for treating RSV.

A research team led by Dr. Richard Plemper from Georgia State University has been searching for broad-spectrum antivirals. These are drugs that can inhibit many different types of viruses. If a broad-spectrum antiviral were approved for human use, it could potentially be used quickly to help fight future pandemics.

The researchers have been testing whether drugs related to molnupiravir might be able to serve as broad-spectrum antivirals. They began with molnupiravir because it is active against RSV as well as SARS-CoV-2.  In a new study, they focused on one related compound called 4’-fluorouridine, or 4’-FIU.

The work was funded by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). Results were published on December 2, 2021, in Science.

In studies in cells, 4’-FIU interfered with the ability of RSV to copy itself without altering the metabolism of the cells. It also interfered with SARS-CoV-2 infection as well as infection by several other viruses with pandemic potential, such as avian influenza.

Further experiments showed that 4’-FIU works by stalling the proteins that RSV and SARS-CoV-2 use to copy themselves. This type of protein, called an RNA-dependent RNA polymerase (RdRP), is used by many types of virus.

In human airway organoids—3-D models of human lung tissue—4’-FIU treatment after RSV infection almost eliminated the virus from airway cells. Based on these results, the team next tested the drug in animals.

When mice were given the drug either a day before or up to a day after infection with RSV, viral replication in the lungs was reduced and pneumonia didn’t occur. Similar results were seen in ferrets infected with SARS-CoV-2, including the alpha, gamma, and delta variants. When 4’-FIU was given 12 hours after infection, the amount of virus found in the nose was reduced by almost three orders of magnitude. Shedding of infectious virus particles ceased completely by 3 days after infection.

“There is an urgent need to expand the therapeutic arsenal against SARS-CoV-2, and 4’-FIU has strong potential to become an additional therapeutic option,” Plemper says.

4’-FIU could potentially be given as a pill once a day, making it an attractive candidate for treatment outside a hospital setting. Early studies of the safety of 4’-FlU in people are now being planned.

—by Sharon Reynolds