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Drug Discovery


Plitidepsin, a molecule from sea squirts, could be a COVID-19 antiviral

The compound kills SARS-CoV-2 in cells by targeting host proteins instead of viral proteins

by Bethany Halford
January 28, 2021 | A version of this story appeared in Volume 99, Issue 4

Plitidepsin, a natural product made by sea squirts and developed by PharmaMar as the anticancer drug Aplidin, could be used as a COVID-19 antiviral. Researchers found that the compound is over 27 times as potent as the antiviral remdesivir (marketed as Veklury by Gilead Sciences) at killing SARS-CoV-2, the virus that causes COVID-19, in cells. It also prevented SARS-CoV-2 from replicating in the lungs of mice (Science 2021, DOI: 10.1126/science.abf4058).

Structure of plitidepsin.

Nevan Krogan of the University of California, San Francisco, led the research along with Kris M. White and Adolfo García-Sastre at Icahn School of Medicine at Mount Sinai. Krogan says that while others looked for drugs that could target the SARS-CoV-2 virus’s proteins, his team wanted to see which human proteins the virus needs to infect cells and which compounds block those proteins.

They landed on eEF1A, a protein that cells use to make other proteins, and its inhibitor plitidepsin, which is approved in Australia for treating multiple myeloma. SARS-CoV-2 hijacks eEF1A to make its own proteins, Krogan says, so plitidepsin prevents the virus from making the proteins it needs.

An advantage to targeting human proteins like eEF1A is that they won’t quickly mutate to evade a drug, the way viral proteins do. But targeting a host protein can lead to toxicity—a problem associated with plitidepsin’s use in cancer. Krogan says that the dose of plitidepsin required to kill SARS-CoV-2 is small compared with that used to treat cancer, and it would be used only for a short period—unlike cancer chemotherapy, which can last for weeks or months.

Sina Bavari, an expert in antiviral therapies and founder of Edge BioInnovation Consulting and Management, says that as new SARS-CoV-2 variants emerge, scientists need to consider other approaches to killing the virus, including targeting host proteins. He says that while preliminary plitidepsin data are encouraging, he would like to know how effective the drug is when given after SARS-CoV-2 infection and how soon it must be given.

PharmaMar has completed Phase 2 trials of plitidepsin to treat COVID-19 and is in discussions with regulatory agencies to begin Phase 3 trials.



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