The study is among existing drugs for COVID-19 treatments that may have emerged to another promising candidate – a cancer drug that appears to perform better than remdesivir approved by Gilead Sciences. against the SARS-CoV-2 virus behind the infection.
In a new study published in Science, researchers from the Icahn School of Medicine at Mount Sinai and the University of California, San Francisco found in preclinical tests that plitidepsin was the Spanish drug dealer PharmaMar, approved under the brand name Aplidin in some countries for multiple myeloma nearly 30 times more powerful than remdesivir.
Furthermore, in a separate paper posted on the preprint site of bioRxiv magazine, the researchers showed that the drug had comparable antiviral activity against the original strain of SARS-CoV-2 and the drug. a new, more infectious version B117, first discovered in the UK
Based on the positive results, PharmaMar stated that it is in discussions with regulatory bodies about initiating phase 3 clinical trials of plitidepsin in COVID.
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Plitidepsin is derived from Aplidium albicans, a sea squirt found off the coast of Spain. It was originally intended to target human protein eEF1A, and that expression can lead to cancer-causing cell signaling.
The team led by Icahn previously found that targeting some host proteins involved in gene-to-protein translation machinery – which is essential for the reproduction of many viral pathogens – could inhibit SARS- CoV-2. That finding tested plitidepsin.
In the new study, the scientists confirmed that plitidepsin actually works against SARS-CoV-2 by inhibiting eEF1A, which interacts with the nucleocapsid (N) protein of the coronavirus during infection.
In studies in human cells, plitidepsin showed 27.5-fold more potent anti-SARS-CoV-2 activity than remdesivir. As remdesivir was cleared by the FDA to treat COVID-19, the researchers tested plitidepsin with the drug Gilead. Their analysis suggested that plitidepsin has an “additive effect” on remdesivir.
The researchers also tested the drug in two different mouse models. In mice given plitidepsin shortly before infection with SARS-CoV-2, the drug significantly reduced viral loads and inflammation of the lungs compared with controls. Plitidepsin induced a reduction in viral loading similar to remdesivir’s, but the cancer drug was better at relieving lung inflammation, the team said.
Plitidepsin has one potential benefit over traditional antivirals such as remdesivir, the team said. By targeting the host protein rather than viral proteins, plitidepsin may counteract drug-induced mutations.
In the second study, the team tested plitidepsin against the more potent B117 version of SARS-CoV-2. The drug showed similar antiviral activity to both the early-line virus and the mutated version in gastrointestinal and human lung epithelial cell layers, and was significantly more potent than remdesivir against both viruses, the team found .
Repeating existing drugs has become a popular strategy among scientists looking for potential COVID-19 treatments. Several other cancer drugs have been proposed to directly inhibit the virus or to reduce the false relapsing response resulting from SARS-CoV-2 infection.
PTC Therapeutics is testing its investigative DHODH inhibitor PTC299 in a phase 2/3 test based on the belief that the drug can both inhibit viral reproduction and inhibit inflammatory molecular production. AstraZeneca previously evaluated its Calquence therapy BTK blood cancer in COVID-19, but the drug failed to reduce mortality rates or respiratory failure.
PharmaMar already has advanced phase 1/2 data for plitidepsin in COVID-19. In October, the company reported that the APLICOV-PC (PDF) trial showed that plitidepsin achieved a significant reduction in viral loading in hospitalized patients, and a striking correlation was observed between the reduction in viral loading and improvement. clinical, among other metrics.
“We believe that our data and initial positive results from the PharmaMar clinical trial suggest that plitidepsin should be strongly considered for extended clinical trials for the treatment of COVID-19,” the Mount Sinai-UCSF team wrote in the Science study. .