Plitidepsin Outperforms Remdesivir in COVID-19 Preclinical Models

Researchers from Icahn School of Medicine at Mount Sinai and the University of California, San Francisco found in preclinical experiments that Spanish drugmaker PharmaMar’s plitidepsin, approved under the brand name Aplidin in some countries for multiple myeloma, was almost 30 times more potent than remdesivir.

Plitidepsin derived from Aplidium albicans, a sea squirt was meant to target the human protein eEF1A. The scientists confirmed that plitidepsin indeed worked against SARS-CoV-2 through inhibition of eEF1A, which interacts with the coronavirus’s nucleocapsid (N) protein during infection. Studies in human cells revealed that plitidepsin showed anti-SARS-CoV-2 activity that was 27.5-fold more potent than that of remdesivir. The drug was also tested in mouse models. In mice that got plitidepsin shortly before being infected with SARS-CoV-2, the drug significantly reduced viral load and lung inflammation compared with controls.

Plitidepsin prompted a reduction in viral load that was on par with remdesivir’s, but the cancer drug was better at relieving lung inflammation, the team reported. By targeting the host protein rather than viral proteins, plitidepsin could potentially avoid the drug resistance that can result from mutations. The team also tested plitidepsin against the highly transmissible B117 variant of SARS-CoV-2. The drug showed similar antiviral activity against both the early-lineage virus and the mutated version in both human gastrointestinal and lung epithelial cell lines. 

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