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Why developing antivirals to fight COVID-19 is such a challenge

COVID-19 coronavirus
Posted at 11:10 AM, Mar 19, 2021
and last updated 2021-03-19 11:10:45-04

SAN DIEGO — Scientists have made big strides in the fight against COVID-19, but there is still only one fully approved treatment — and it’s not a breakthrough cure.

Currently, remdesivir is the only therapeutic drug approved for emergency use with COVID-19.

Outside of a few blends of monoclonal antibodies that have emergency authorizations, remdesivir is our only FDA-approved antiviral that can attack SARS-CoV-2 head-on. Other treatments try to resolve the cascade of domino effects that come with severe disease — like out-of-control inflammation — not the virus itself.

Studies show remdesivir shortens illness time in hospitalized patients, but it doesn’t improve survival rates. That’s why scientists continue to race to develop better, stronger antivirals that can save lives.

UC San Diego virologist Dr. Davey Smith is helping lead the charge.

Smith oversees an important section of clinical trials created under Operation Warp Speed called ACTIV-2.

“Our job is to find therapies for people with early COVID, so to prevent people from getting into the hospital. That's our whole job,” Smith said.

The team is currently enrolling volunteers to study five promising potential drugs. A sixth drug will be added later this month, Smith said.

This arm of the ACTIV trials is focused on treatments for recently diagnosed patients — and is seeking information from people who have tested positive for COVID-19 in the last six days.

Developing drugs for a new pathogen is always tough work, but doing so in a pandemic adds another layer of complex infection control procedures, Smith said.

In many ways, developing antivirals is harder work than developing antibiotics to fight bacteria.

For one, bacteria are big living cells that are easier to target. There are plenty of natural antibiotics in the environment — lots of bacteria combat other bacteria, Smith noted.

Classes of bacteria share characteristics that can be attacked by a single drug. That's why doctors prescribe azithromycin, for example, for a range of infections.

Viruses, on the other hand, hijack human cells. Treatments have to be narrowly tailored to attack the virus and not healthy cells. Coronaviruses in particular present their own challenges.

In general, viruses can mutate more efficiently.

“You would expect the virus to try to find a way to get around any drug that you use. And what we have to do as scientists in these clinical trials is to figure out which drug causes less of that, or maybe use more than one drug,” Smith said.

Smith's team is currently testing new kinds of manufactured antibodies, along with an inhalable drug and a pill designed to interfere with the virus’ ability to replicate.

Scientists often do that by finding ways to add junk code to the virus’ RNA — similar to installing malware on a computer to crash the system. But unlike some other viruses, SARS-CoV-2 has a tricky defense system.

It essentially has a viral spellcheck.

“This coronavirus has a proofreading mechanism to go back and say, ‘Aha! You tried to trick me and put that fake [RNA] base in there. I'm going to take it out and put a regular one in,’” Smith said.

Still, researchers have several promising therapies in the works and Dr. Smith expects new ones on the market this year.

But scientists can’t do it alone. They need people to sign up for clinical trials.

This story was originally published by Derek Staahl on KGTV in San Diego.

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Data from The Center for Systems Science and Engineering at Johns Hopkins University.