The race to find covid-19 drug treatments that really work
But antibody therapies have disadvantages. They are expensive and should be given by infusion or injection. This makes them few options for many middle- and low-income countries. And they might not behave well against some variants in circulation. In fact, on June 25, the FDA paused in the distribution of Lilly’s antibody cocktail across the country due to the growing prevalence of two primary variants that did not appear to respond to the drugs.
When it comes to antiviral drugs, which disrupt the virus’s ability to replicate, even fewer options are available. Remdesivir is the only drug approved to treat covid-19, largely because it was one of the few candidates that had been tested for safety in humans when the pandemic struck, so it had a start. But how well it works is still an open question. Some studies have found it to shorten the length of the disease, while others suggest that it has little impact. The World Health Organization does not recommend its use.
Antiviral development is delayed for a variety of reasons. Until covid-19, companies did not have much financial incentive to produce these drugs. Existing antivirals target only 10 viruses, and half of them treat HIV. Chronic infections require longer treatments and thus earn more money. “If there isn’t an obvious market for a therapy, then generally speaking, they shouldn’t invest in these types of therapies,” says John Bamforth, interim executive director of READDI, a public-private partnership at the University of North Carolina at Chapel Hill founded to develop new antivirals.
There are also a number of scientific obstacles. To inhibit replication, a drug binds to some essential viral protein or enzyme and blocks its activity without damaging the host cell. But unlike bacteria, viruses rely on the machine in the cells they inhabit to copy themselves, so they have few proteins of their own. And even when researchers encounter a compound that works, its effectiveness tends to be short-lived because viruses are constantly evolving.
Some researchers, including those at READDI, are working on drugs that target cellular proteins crucial for viral replication. Most antivirals only work on a single virus. The hope is that these compounds will be effective against entire families of them. They may also be less likely to lead resistance.
But new therapies take longer to develop. That’s why the fastest way to get drugs off the shelves is to reject compounds that have already been approved. They have been tested for safety, and there are fewer regulatory barriers to obtaining a new approved use for an existing drug. DNDi tests a variety of compounds existing in a clinical trial called ANTI-VOC. The latest study looks at the antiparasitic drug nitazoxanide combined with an inhaled steroid. “The consensus that emerges is that you need a strong antiviral or a combination of antivirals with different mechanisms of action, combined with one type of anti-inflammatory,” says Cohen.