A UCSF research team has discovered a potential revolutionary treatment for COVID-19, although it is a cancer drug made by a Spanish company that has not yet been approved for any use in the United States.
The drug is called Aplidin (generic name: plitidepsin), and is a compound originally derived from another found in a bizarre sea creature found near Ibiza, called Aplidium albicans. As the team explains in a new report in the journal Science, plitidepsin has been shown to dramatically inhibit the replication of SARS CoV-2, also known as coronavirus, and may in fact be 30 times more effective as an antiviral treatment than remdesivir, which has been used on an emergency basis in patients in clinical settings since last winter.
The team that discovered the new treatment was led by UCSF systems biologist Nevan Krogan, and it appears to be potentially the biggest success of a project that started last February to isolate existing drugs and compounds that may work as antiviral treatments. As we reported last May, Krogan’s team at UCSF’s Quantitative Biosciences Institute abandoned everything they were working on last winter to focus on COVID-19 and, in April, identified 10 existing drugs that showed promise in treating the new disease .
Scientists from San Francisco and other teams around the world who participate in the same effort found two human proteins that appeared to be the key in the fight to stop the coronavirus’s ability to replicate within people, Sigma R1 and Sigma R2, and its drug research initially focused on them. Aplidine acts on the human protein known as eEF1A and, as it focuses on the human part of the equation and not on the virus, it must remain effective as long as the virus mutates.
And the project is highlighting something that scientists have long emphasized about the importance of maintaining biodiversity in the world’s oceans and elsewhere. The marine invertebrate from which this compound is derived is an ascidian or ascidian that looks “a little like a disembodied brain”, as the Chronicle explains. The drug actually belongs to a Spanish company founded by a diver, Pharma Mar, and has been approved in Australia for the treatment of blood cancer known as multiple myeloma. It has also been used in the EU as a treatment for lymphoblastic leukemia.
The drug is in Phase 2 clinical trials in Spain, during which it was tested on 45 seriously ill patients with COVID. Based on data from the first 27 of these patients, the drug significantly reduced the amount of time people spend in the hospital, with 81% going home after 15 days, compared to a typical rate of less than 50%. And according to a separate article, Aplidin appears to be effective against the UK virus variant as well.
“We need some new weapons in the arsenal,” Krogan told the Chronicle. “This is by far the best thing we’ve seen.” Krogan says the research team for this drug was also led by virus expert Adolfo García-Sastre, based at the Icahn School of Medicine at Mount Sinai Hospital in New York.
UCSF infectious disease specialist Dr. Peter Chin-Hong says that if the drug emerges from a Phase 3 trial still looking good, it is likely to be part of a “cocktail” of therapies for COVID. Doctors across the country are treating patients with a remdesivir cocktail and the steroid dexamethasone, and in Australia, Aplidine is used in combination with dexamethasone to treat multiple myeloma.
Aplidin has yet to undergo further broad-based Phase 3 clinical studies, which are expected to take place in Spain and the United States. And it is not yet known how long it will last – if it is as effective as the first tests suggest – before which drug becomes widely available here.
Top image: An image of sea water Aplidium albicans found in the Balearic Islands, from which the synthetic drug Aplidin is derived. Photo via Pharma Mar