A popular heartburn medicine doesn’t work as a COVID-19 antiviral

An over-the-counter heartburn remedy probably won’t directly stop coronavirus infections, a new study suggests.

Anecdotal reports from China suggested people hospitalized with COVID-19 who were taking famotidine (sold under the brand name Pepcid) had better outcomes than people who took a different type of antacid called a proton pump inhibitor. But famotidine has no direct antiviral activity against SARS-CoV-2, the virus that causes COVID-19, according to preliminary results reported July 15 at bioRxiv.org.

Those findings, which have not been reviewed by other scientists yet, suggest famotidine won’t help prevent coronavirus infections or illness. But they don’t rule out that the drug might help in other ways, says Mohsan Saeed, a virologist at Boston University School of Medicine. “We’re not challenging that famotidine might help,” he says. “We’re saying that the mechanism of action is not antiviral.”

The result isn’t a complete surprise. “A compound of this nature having any role in infectious disease is kind of a head-scratcher,” Saeed says. But a couple pieces of evidence had hinted that it might help against the virus.

Besides the reports out of China, two studies using computer simulations of coronavirus proteins predicted that famotidine might dock with and inhibit important viral enzymes called proteases that help the virus replicate. Based on those findings, Northwell Health in the New York City area began a clinical trial to test the antacid against the coronavirus in people.

“We were kind of surprised, because there is no laboratory evidence to show that this compound might have some effect,” Saeed says.

The data that originally suggested benefits from famotidine aren’t strong enough to justify basing treatments on the drug, says Tobias Janowitz, an oncologist and biomedical scientist at Cold Spring Harbor Laboratory in New York, who was not involved in the study. “Everything that has been published so far cannot be considered evidence for clinical efficacy,” he says. That includes a small study Janowitz was involved in which also found hints that over-the-counter Pepcid might improve symptoms for some people diagnosed with COVID-19.

Just “because a statistical association exists in these anecdotal reports doesn’t mean it is actually doing anything,” Shmuel Shoham, an infectious disease specialist at Johns Hopkins Medicine said June 26 during a news conference announcing the Infectious Diseases Society of America’s revised treatment guidelines. The infectious disease society doesn’t recommend taking famotidine as a coronavirus treatment outside of a clinical trial.

To test famotidine’s antiviral activity, Saeed teamed up with Ali Munawar, cofounder and chief executive of Boston-based Bisect Therapeutics, Inc. Munawar’s lab did two different biochemical analyses to test whether Pepcid can bind to viral proteases as the computer simulations had predicted. Neither test showed any sign of binding.

But it was still possible that the antacid might work in other ways against the protease enzyme. So the team conducted separate analyses of enzyme activity which found no protease inhibition at all.

The team also tested whether famotidine could stop the coronavirus from infecting monkey cells or human lung cells grown in lab dishes. “We did not see any effect on viral infection,” Saeed says. By comparison, the antiviral drug remdesivir “nicely inhibited viral replication,” he says (SN: 7/13/20).

While the work has not yet been vetted by other scientists for publication in a scientific journal, the results are in line with unpublished findings from Janowitz’s Cold Spring Harbor colleagues Leemor Joshua-Tor and Nicholas Tonks who found that famotidine doesn’t inhibit the proteases as predicted, he says.

Researchers say there is still a chance that famotidine might help slow the hyperactive immune system reactions known as cytokine storms, which do damage in some severely ill COVID-19 patients (SN: 7/2/20).

“We’re not shutting the door on this being an effective therapy,” Shoham said, but doctors should not prescribe the drug to treat COVID-19 and people should not take over-the-counter Pepcid as a coronavirus remedy. The antacid needs further study in randomized clinical trials, he said. Janowitz and colleagues are planning just such a trial.