Scientists hunt for antiviral drugs to fight COVID-19

Antiviral drugs can be a key pandemic-fighting tool, but so far there's only one approved in the U.S. for SARS-CoV-2, the virus that causes COVID-19.

Why it matters: Because some people won't get vaccinated, and because there will likely be new variants of the virus, we'll need effective treatments — including antivirals, former FDA commissioners Scott Gottlieb and Mark McClellan wrote earlier this week in the Wall Street Journal.

• "Hopefully we can get ahead of [emerging variants], but given that some virus will be circulating, it is important to have therapeutics," says Esther Krofah, executive director of the Milken Institute's FasterCures center.

Driving the news: This week, Merck and Ridgeback Biotherapeutics said the antiviral molnupiravir "significantly reduced infectious virus in subjects in a mid-stage study after five days of treatment," WSJ reported.

• Merck is expecting interim results from two later-stage clinical trials looking at whether the drug prevents hospitalization and death from the virus. Those studies will help determine whether the drug has a clinical benefit.
• On Tuesday, Pfizer presented details about an oral antiviral it developed from scratch during the pandemic, Chemical & Engineering News reports.

How it works: Antivirals stop a virus from reproducing — either as it attaches to a person's cells, uses those cells to make copies of itself, or exits the cells for the rest of the body.

• Some antivirals target proteins in the virus itself. Others inhibit machinery in the host cell that the pathogen relies on to replicate.
• The catch is that all have to be given early in the course of the disease to prevent the virus from getting a foothold and spreading in the body.

Where it stands: So far, remdesivir — a drug investigated earlier to treat Ebola and other diseases — is the only antiviral approved in the U.S. for COVID-19.

• While there is evidence it helps speed recovery and prevents the disease from progressing, it doesn't prevent death from the virus. And because it is administered via an IV, the drug's use is limited to people who have been hospitalized — and are therefore further into their illness.
• 31 other antivirals are being investigated, according to the Milken Institute's COVID-19 tracker.
• A goal for SARS-CoV-2 is to develop an equivalent to Tamiflu, an oral antiviral that can be taken at home after someone is exposed but before symptoms appear, says Armand Balboni, CEO of Appili Therapeutics, which is studying the effectiveness of another antiviral — favipiravir — approved in Japan for treating new flu strains and in Russia and India for COVID-19.

"Antivirals are very challenging to develop," says Kris White of Mount Sinai, who is investigating plitidepsin, a drug already approved in Australia to treat multiple myeloma, as an antiviral for SARS-CoV-2.

• Because they rely on hosts to reproduce, viruses have few proteins of their own that antivirals can act on, he points out.

What to watch: There are concerns that current vaccines and antibody treatments could be less effective against emerging SARS-CoV-2 variants because they act on proteins on the surface of the virus that can mutate quickly.

• Antivirals target key machinery for virus replication that tends to be more stable, but resistance to antivirals can develop too, White says.
• For example, some influenza strains are resistant to antiviral drugs.
• An antiviral that targets the host cell's proteins versus the virus' proteins is one approach to try to minimize resistance. Combining antivirals, similar to what is done to treat HIV, is another avenue under investigation for COVID-19.

The big picture: "We need to move from a just-in-time to just-in-case approach" for developing therapies in order to prepare for the next pandemic, says Balboni, who specialized in pandemic response and infectious disease for almost two decades with the U.S. military.