The virus that causes COVID-19, SARS-CoV-2, cannot grow and spread through the body without the help of a protein called polymerase. Now researchers at Columbia University and the University of Wisconsin-Madison have identified several molecules that interfere with the polymerase reaction—and some of them are already FDA-approved to treat other viruses.
The researchers identified five existing drugs that can shut down the polymerase reaction, they reported in the journal Antiviral Research. They include medicines used to treat HIV, cytomegalovirus, and hepatitis B.
SARS-CoV-2 uses polymerase to copy its genome inside of infected cells. But if that process could be stopped, the immune system would kick into gear and destroy the coronavirus, the researchers reasoned.
The team started their quest to interrupt the polymerase reaction by investigating an active ingredient of Gilead’s hepatitis C blockbuster Sovaldi. They analyzed a triphosphate that had been shown in previous experiments to halt the polymerase reaction of SARS-CoV-2, which sparked an outbreak in the early 2000s.
From there, they selected 11 compounds that they thought would have the best features to inhibit the polymerase of SARS-CoV-2. All but three did the job, they reported.
The five FDA-approved drugs that could work against COVID, the team reported, include ViiV’s Ziagen and Bristol Myers Squibb’s Zerit, both used to treat HIV; Roche’s Valcyte and Gilead’s Vistide for cytomegalovirus; and BMS’ Baraclude for hepatitis B.
In the search for COVID-19 remedies, several researchers and biopharma companies have drawn inspiration from previous studies of the first SARS virus. They include Ridgeback Biotherapeutics, which is testing its antiviral, EIDD-2801, in both hospitalized and non-hospitalized COVID patients. EIDD-2801 has shown activity against other RNA viruses, including SARS and MERS.
Gilead’s remdesivir, already FDA-approved to treat COVID-19, was originally being studied to treat hepatitis C (HCV) and respiratory syncytial virus (RSV). Other companies that are repurposing drugs initially developed against other diseases are Pinpoint Therapeutics and Orpheris.
The next step for the Columbia and University of Wisconsin researchers is to perform cell-culture studies to demonstrate the potency of the five FDA-approved antivirals against COVID-19. From there, the most effective of the drugs—or modified versions of them—could advance to further studies, they suggested.