The antiviral agent plitidepsin (Aplidin) can block growth of the SARS-CoV-2 virus in different cell lines and in the lungs of mice. The SARS-CoV-2 virus is the strain that causes COVID-19.
The antiviral activity of plitidepsin was nearly 28-fold stronger than that of remdesivir against SARS-CoV-2. The researchers also note that the two drugs act on different targets. Remdesivir plus plitidepsin, if approved for use, could provide an additive effect when given together.
"The potency of the inhibitor is quite amazing," said senior author Adolfo Garcia-Sastre, PhD.
Given as a preventive measure, plitidepsin also reduced reproduction of the virus in the lungs of mice.
The study was published online January 25 in Science.
The results suggest "that plitidepsin should be strongly considered for expanded clinical trials for the treatment of COVID-19," the researchers note.
Still, it's early. "We have found a potent inhibitor of SARS-CoV-2 replication, but clinical trials are still needed to find whether it provides a benefit to patients," added Garcia-Sastre, director of the Global Health Emerging Pathogens Institute at Icahn School of Medicine at Mount Sinai in New York City.
Because the drug is an antiviral agent, "it needs to be given during the active replication phase of COVID-19. Similar to remdesivir and all other antiviral drugs, the sooner it is given to you, the better chance it has of being effective," lead author Kris M. White, PhD, assistant professor of microbiology, Icahn School of Medicine at Mount Sinai, told Medscape Medical News.
The investigators said that current treatments for patients with COVID-19 include oxygen treatment, ventilation, remdesivir, and the steroid dexamethasone. They add that remdesivir in particular has shown it doesn’t work that well and dexamethasone is a steroid that does not directly keep the virus from reproducing.
"This leaves a continued need for the development or repurposing of antiviral drugs for the treatment of COVID-19," they note.
Robin Ferner, MD, said the drug also reduced the amount of virus in mice if they received it before getting infected.
Ferner’s honorary posts include professor of clinical pharmacology at the University of Birmingham in the United Kingdom and associate professor at University College London.
Ferner raised an issue regarding potential side effects. "The drug has been used experimentally to treat patients with multiple myeloma, but adverse effects are common and included raised liver enzymes" in a 2019 study, he said.
Dexamethasone is also commonly used to treat people with multiple myeloma. "This has led to plitidepsin already having an established safety profile with concurrent dexamethasone treatment and should allow for clinicians to treat with both drugs if warranted," the researchers note.