This coronavirus drug is 30 times more potent than remdesivir, and it works against mutated strains – BGR

• Researchers believe that a promising treatment for the coronavirus is 30 times more potent than remdesivir and may work against new, highly infectious mutations.
• Plitidepsin, an anticancer drug, may speed up recovery in patients, and according to a study a few months ago.
• A team led by UCSF has done two studies, indicating that the drug is more effective than remdesivir and can kill the UK mutation.
• Plitidepsin does not directly target the virus, but rather a human protein that the virus needs in order to replicate.

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The first drug to be approved for treatment with COVID-19 was remdesivir, but it has not proven to be the key drug that would help doctors save lives or beat the pandemic. The drug works in some patients, but it’s not the definitive cure that the world needs besides vaccines to end the pandemic. Several teams of researchers are looking for new therapies to stop the coronavirus from killing so many people, with a UCSF-led group now identifying an anticancer drug that appears to be nearly 30 times more potent than remdesivir.

The drug is called Aplidin (plitidepsin), and we learned about this several months ago when Spanish researchers showed that the drug was able to block the replication of the virus. Plitidepsin helped patients recover much faster than others who received standard care, and 81% returned home within 15 days, a significant improvement over the typical return rate of 47%. Now, more recent studies also show another key advantage the drug may have over other COVID-19 therapies: It works against new, highly infectious mutations in SARS-CoV-2. This is because rather than attacking the virus itself, the drug affects a specific protein in human cells that the new coronavirus must replicate.

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The Spanish company Pharma Mar has developed plitidepsin, extracted from a marine jet called Albicans ecology. The drug was approved in 2018 to treat multiple myeloma, but only after Pharma Mar dealt with a controversy at home. The European Union blocked the approval of plitidepsin in 2017, saying the risks outweighed the benefits – but Pharma Mar was able to reverse the decision.

“We need new weapons in the arsenal,” said Nevan Krogan, molecular biologist at UCSF. SF Chronicle about plitidepsin. “This is by far the best thing we’ve seen.”

Researchers from the Institute of Quantitative Biosciences at UCSF (the QCRG group) worked with Mount Sinai and the Institut Pasteur in Paris. QCRG researchers studied the coronavirus last year, seeking to understand how it works at a microscopic level after infecting the human cell. The aim of the project was to find a way to block the virus. Among the thousands of drugs and experimental compounds tested in the laboratory, plitidepsin stood out.

Scientists used extremely low concentrations of the drug to kill the virus in lung cells developed from human and monkey tissue. They then infected mice with the coronavirus and treated them with plitidepsin, finding that the drug cleared the virus from their bodies. Plitidepsin did not attack the virus directly like remdesivir or other drugs and vaccines. Instead, the virus blocks the activity of a specific protein inside cells (eEF1A), without which the virus cannot replicate.

The full study was published in Science.

The researchers did not stop there, however. They have teamed up with a lab in the UK to test plitidepsin against variant B.1.1.7 of the virus, the UK mutation that is now dominant in the country. They found that the drug could kill this strain as well and was more potent than remdesivir. This study has also been published online, but in a non-peer reviewed format.

The team believe the drug would continue to work against other mutations due to the eEF1A protein it targets. “If you get a drug that targets a human protein, it would be incredibly difficult for the virus to mutate to not depend on it,” Krogan said.

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As the EU expressed concern about the side effects of plitidepsin in cancer patients, Pharma Mar said The Chronicle that patients with COVID-19 would require significantly lower doses than cancer patients. They would also need to take it for just three days instead of months. Side effects on patients with COVID-19 have been minimal so far.

While plitidepsin shows promise and could prove to be a drug that further reduces deaths from COVID-19, strict human testing will need to be done before the drug can be approved for treatment with COVID-19. Phase 3 trials are planned in Spain and the United States, according to Pharma Mar.