How Sea Squirts are Helping Us Fight COVID-19

Written by Krish Ajmani and Zaid Bustami

The sea squirt species Aplidium albicans is giving us a helping hand in fighting the COVID-19 pandemic. In a recent study published in Science, researchers concluded that plitidepsin, a therapeutic extracted from this species of sea squirt, can potentially be more effective than the antiviral remdesivir for treating COVID-19. Also known by its trade name Aplidin, the drug is already utilized to treat multiple myeloma, a type of bone marrow cancer. After completing studies involving cell cultures and mice, scientists have demonstrated the drug’s additional effectiveness in targeting the coronavirus that causes COVID-19, SARS-CoV-2.

So how does plitidepsin work? It takes advantage of the way a virus uses proteins on its surface that interlock with human receptor proteins in order to infiltrate and infect a host cell. The drug blocks one of these key interactions by inhibiting access to the receptor protein eIF4H that the coronavirus protein SARS-CoV-2 Nsp9 normally binds to. A door with a blocked keyhole cannot be unlocked by a key. Likewise, a cell with an inhibited receptor protein cannot be unlocked by a virus, thereby preventing the microbe from using that cell to replicate and spread.

Plitidepsin is especially important to the development of COVID-19 therapeutics because of its relative high efficacy compared to remdesivir, the only antiviral currently approved by the FDA to treat the disease. Researchers conducting the study remarked,

“The current standards of care include oxygen therapy and ventilation, along with the antiviral remdesivir and the anti-inflammatory dexamethasone. Remdesivir and dexamethasone have each improved patient outcomes in clinical trials…but remdesivir in particular has shown limited efficacy and dexamethasone is a steroid that does not directly inhibit viral replication.”

According to the study, plitidepsin is 27.5 times more effective than remdesivir when tested in cell cultures. In addition, plitidepsin was found to be twice as effective as remdesivir at preventing the replication of SARS-CoV-2 in mice and had the added benefit of decreasing lung inflammation. This result highlights how plitidepsin holds the potential to be an effective monotherapy (a treatment involving only one drug) for COVID-19. The drug has already seen efficacy in clinical trials: Aplidin’s manufacturer PharmaMar has concluded successful phase I/II clinical trials with phase II/III trials expected to be underway soon.

This study has major implications for public health amidst the ongoing pandemic. The therapeutics used by the vast majority of hospitals have been mostly restricted to the two drugs mentioned above: remdesivir and dexamethasone. Both, however, are severely limited in their overall effectiveness in treating those afflicted with COVID-19. In addition to improving treatment outcomes, a second antiviral remedy would ease the healthcare system’s precarious reliance on the supply of a single therapeutic. According to an article by Janice Tanne, a correspondent for the BMJ, nearly 40 US hospitals faced remdesivir shortages between July and September of last year alone. The second antiviral could also boost the flexibility of patient care by allowing providers to select a treatment option that best suits their patients rather than relying on a single antiviral treatment.

Vaccines continue to roll off the production line in multiple factories. However, it will still take time for these vaccines to be sufficiently distributed to the public for herd immunity to develop. The development of new treatments for those with COVID-19 is thus pertinent and necessary for saving as many lives as possible, especially while vaccinations are still being administered. And while it also may take time for new COVID-19 therapeutics like plitidepsin to become approved for use in patients, research in this field is still key to learning more about how SARS-CoV-2, a virus we still have much to learn about, infects and affects the body.

Today’s research into COVID-19 therapeutics is both dynamic and encouraging. The sea squirt extract plitidepsin has proven to hold great potential, and its potency alone warrants greater study into its effects. Until scientists can fully determine its efficacy, we can only hope that a humble sea creature may prove to be a critical asset in our struggle against COVID-19.

Photo by Andrea Izzotti

Further Reading:

Plitidepsin: a Repurposed Drug for the Treatment of COVID-19

Antiviral Therapy | COVID-19 Treatment Guidelines (nih.gov)

Final report confirms remdesivir benefits for COVID-19 | National Institutes of Health (NIH)