But antibody therapies have drawbacks. They’re expensive and must be given via infusion or injection. That makes them poor options for many low- and middle-income countries. And they may not perform as well against some circulating variants. In fact, on June 25 the FDA paused distribution of Lilly’s antibody cocktail nationwide because of the increasing prevalence of two variants of concern that don’t seem to respond to the medicines.
When it comes to antiviral drugs, which interrupt the virus’s ability to replicate, even fewer options are available. Remdesivir is the only such medication approved to treat covid-19, in large part because it was one of the few candidates that had been tested for safety in humans when the pandemic hit, so it had a head start. But just how well it works is still an open question. Some studies have found it to shorten the length of the illness, while others suggest it has little impact. The World Health Organization does not recommend its use.
Antiviral development has lagged for a variety of reasons. Until covid-19, companies didn’t have much of a financial incentive to produce these drugs. The antivirals that do exist target just 10 viruses, and half of them treat HIV. Chronic infections require lengthier treatments and thus make more money. “If there is not an obvious market for a therapeutic, then generally speaking, they’re not going to invest in those types of therapeutics,” says John Bamforth, interim executive director of READDI, a public-private partnership at the University of North Carolina at Chapel Hill founded to develop novel antivirals.
There are also a number of scientific hurdles. To inhibit replication, a drug has bind to some essential viral protein or enzyme and block its activity without harming the host cell. But unlike bacteria, viruses rely on the machinery inside the cells they inhabit to copy themselves, so they have few proteins of their own. And even when researchers do come across 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 medicines that target cellular proteins crucial for viral replication. Most antivirals work on only a single virus. The hope is that these compounds would be effective against entire families of them. They may also be less likely to drive resistance.
But novel therapies take more time to develop. That’s why the quickest way to get drugs on the shelves is to repurpose compounds that have already been approved. They have been tested for safety, and there are fewer regulatory hurdles to getting a new use approved for an existing drug. DNDi is testing a variety of existing compounds in a clinical trial called ANTI-COV. The latest study looks at the anti-parasite medicine nitazoxanide combined with an inhaled steroid. “The consensus that is emerging is that you would need a strong antiviral or a combination of antivirals with different mechanisms of action, combined with some kind of anti-inflammatory,” Cohen says.