Drugs for Coronavirus: What May or May Not Work

David Levine

On April 29, the world got what may have been the first good news about the coronavirus pandemic. The National Institute of Allergy and Infectious Diseases announced that hospitalized patients with advanced COVID-19 and severe lung disease who were treated with an antiviral drug called remdesivir recovered faster than similar patients who received a placebo.

A randomized, controlled trial involving 1,063 patients, which began on Feb. 21 and was called the Adaptive COVID-19 Treatment Trial, or ACTT, was the first U.S.-based clinical trial to evaluate an experimental treatment for COVID-19. Preliminary data showed that patients who received remdesivir had a 31% faster time to recovery than those who received the placebo. In specific terms, the median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received the placebo. Recovery was defined as being well enough to be discharged from the hospital or to return to normal activity.

The study also suggested that remdesivir, a broad-spectrum antiviral treatment that is given through a daily infusion for 10 days, may improve the odds of survival. The drug group had a mortality rate of 8% versus 11.6%; this difference was not statistically significant but still encouraging.

That has left many health experts with their fingers crossed. "Based on what the NIH tells us, this drug has promise and it works," says Thomas Lodise, a clinical pharmacist at the Stratton VA Medical Center in Albany, New York, and a professor at the Albany College of Pharmacy and Health Sciences.

But it is not the end of the search for drug treatments for the coronavirus -- not by a long shot. "Patients still die (on remdesivir), and that tells me we still need other therapies," Lodise says. "It tells me that we can identify remedies to build on this. It is not the ultimate treatment, but it's a promising lead."

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Drug Cocktails May Be the Answer

Before life can truly return to anything close to normal, researchers will need to create a vaccine and/or treatments that are proven safe and effective through rigorous clinical trials. Because this disease is so new, very few clinical trials have been completed, says Dr. Greg Deye, medical officer in the National Institute of Allergy and Infectious Diseases' Parasitology and International Programs Branch. "At this point there are no drugs that we know will work. There are several classes of drugs that we hope will work and that have a realistic chance of working," Deye says.

Among these are drugs that decrease the replication of the virus, like remdesivir. Other classes of drugs may decrease the body's inflammatory reaction, which can go into hyperdrive when fighting the virus and cause potentially fatal damage to several organ systems. Chloroquine and hydroxychloroquine fall into this category, but research to date has not shown them to have a positive effect against COVID-19.

Indeed, many immunologists believe it will require several drugs used in concert, in what is known as a drug cocktail, to treat the novel coronavirus -- similar to how they treat patients with HIV, the virus that causes AIDS. "I think it is very likely that we will find treatments that will help at various stages of the disease," Deye says. "Probably, none of them will be perfect, but they might help with preventing severe symptoms and deaths. Part of the challenge is that this process usually takes years, and researchers are racing to do it in weeks to months."

There are several studies currently being conducted around the world investigating such drug combinations. According to Reuters, a trial in Hong Kong involved a three-drug combination of the HIV medicine lopinavir-ritonavir, the hepatitis drug ribavirin and the multiple sclerosis treatment interferon beta. This cocktail helped reduce symptoms in patients with mild to moderate COVID-19 infection and lowered the amount of virus in their bodies.

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Viruses Are Hard to Kill

Unlike bacteria, which are often easily and effectively treated with antibiotics, viruses have proved extremely difficult to tame. There are a number of reasons for this. For one, they are incredibly small. SARS-CoV-2 measures 120 nanometers; for comparison, the bacteria E. coli is 16 times bigger and a single red blood cell is 64 times bigger, Lodise says. In addition, drugs often target cell proteins to disrupt how they function. A human cell has about 20,000 proteins, but SARS-CoV-2, the virus that causes COVID-19, has only 32, he says.

That's not all. " Viruses have been around a long time and multiply rapidly in large numbers. This gives them lots of practice at evading host defense mechanisms," Deye says. Viruses are essentially "dead" until they invade a host, where they use that host's own cellular mechanisms to replicate. "So they have fewer of their own processes that we can target with drugs," Deye says. But there are targets -- those few proteins in the virus itself or those in the host cell -- that allow the virus to take hold. "And our experience with infections like HIV, hepatitis C and influenza has given us practice at developing drugs to target these," he says.

Many of the drugs being studied are thus older medicines being "repurposed" to see if they work against SARS-CoV-2. "Drug repurposing is an important area to investigate," Deye says. Most new drugs in development do not pan out, he says. "But reasons for hope are that one reason that (new) drugs fail in development is toxicity. We find that a drug has harmful effects, and each of these (repurposed) drugs has usually already been proven to be relatively safe," he says. "Another reason for hope in this approach is that there are a lot of drugs, so, even if most of them don't pan out, we might get one or two."

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Time Will Tell What Treatments Work

Deye admits it's very hard to know when an effective treatment or cocktail will be available. "I think that within coming months we will know a lot more about the best ways to use existing treatments to help people survive this illness. Development of new treatments and vaccines is slower and might take months to a year or so," he says. Reuters reports that more than 100 potential COVID-19 vaccines are currently in development, and several are already in clinical trials. But the World Health Organization said in April that a workable vaccine was at least 12 months away.

And in the end, there may never be a fully effective vaccine or cure. Only one virus has ever been fully eradicated by vaccination: the small pox virus, Lodise says. The influenza vaccine is only, at best, about 50% effective, he says. "Viruses are very slippery. It's hard getting your hands around managing a viral infection," he says. Lodise believes that, as with the flu, people may still come down with COVID-19 even with a vaccine. "It is likely there will be no panacea, no 100% cure," he says. "We have to look at doing better with treatments."

And as our experience with HIV, hepatitis and other viral infections have shown, that is quite possible. It will just take some time.