The frantic search for COVID-19 treatments has turned up some promising candidates — and many, many more duds. Even some treatments that seemed effective early on, like convalescent plasma therapy, haven’t held up when tested in groups of patients that were big enough to be statistically significant.
While most attention is being paid to new treatments — like the vaccines and therapies currently in clinical trials — a faster win would come if we discovered that a medication already on the market happens to be effective against the SARS-CoV-2 virus. That was the idea behind obvious candidates like remdesivir, an approved antiviral treatment, and dexamethasone, a known anti-inflammatory medication.
But many scientists believe that there could be even better COVID-19 treatments already on the market, if only we knew where to look. They argue that casting a wider net — considering drugs that are not obvious for use against a virus — could lead to new tools for the pandemic response.
How wide a net should we cast? Thanks to advanced, high-capacity computational screening, as well as a wealth of gene activity data, scientists at the University of California, San Francisco, have made a compelling case that any approved drug should be considered. Their efforts to determine which therapies could be repurposed for the pandemic has already turned up a range of promising candidates including some typically used to treat schizophrenia, epilepsy, leprosy, and gout.
At the annual meeting of the American Society of Human Genetics, UCSF’s Tomiko Oskotsky reported on her team’s progress in what she calls a “drug repositioning pipeline” (the data was also posted as a preprint). It’s not the first time UCSF has applied this pattern-matching approach to identify new uses for existing drugs; past successes have led to new candidates for treating pregnant women at risk of preterm birth, among other conditions.
The team uses publicly-available data about gene activity to try to find drugs that might counteract gene activity associated with the COVID-19 immune response. An initial screen led to 102 hits, and scientists ran follow-up functional studies on 16 of the most promising treatments identified. Results of cell-based SARS-CoV-2 studies revealed that 11 of the 16 candidates had significant antiviral potential.
This is preliminary data, but Oskotsky noted that some of these treatments are already moving into clinical trials to see how they fare in humans. Some of the promising candidates include cyclosporine, haloperidol, valproic acid, and clofazimine. And there’s reason to be hopeful beyond Oskotsky’s cell studies: In some clinical reports of COVID-19 patients, it appears that patients who were already taking these drugs for other reasons had better outcomes than patients who weren’t.
“For next steps,” Oskotsky said in her conference presentation, “we’re considering exploring a combination therapy strategy.” It’s possible that combining some of these candidates into a cocktail could trigger an even stronger response.