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An antiviral drug (plitidepsna) produced by the Spanish company Pharmamar and tested in experimental laboratories in France and the United States showed a 99 percent decrease in Sars-CoV-2 viral loads in “in vitro” and “in vivo” experiments, according to a study published Tuesday by the journal Science.
Preclinical studies with this drug, used as an antitumor, were carried out in animal models and showed a promising antiviral efficacy and toxicity profile, according to what was stated by the Spanish company after the publication of the results.
The authors concluded that plitidepsin is “by far” the most potent compound discovered so far. and therefore proposed that it should be tested in more clinical trials to explore it as a treatment for covid-19.
The work was the result of collaboration between the Spanish PharmaMar and the laboratories of researchers Kris White, Adolfo García-Sastre and Thomas Zwaka, in the Departments of Microbiology and Cell, Regenerative and Developmental Biology, at the Icahn School of Medicine of the Mount Sinai (New York); by scientists Kevan Shokat and Nevan Krogan, at the Institute for Quantitative Biosciences at the University of California San Francisco, and by Marco Vignuzzi, at the Pasteur Institute in Paris.
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Specifically, the authors determined that “the antiviral activity of plitidepsin against Sars-CoV-2 is produced through the inhibition of a known target (eEF1A)” and they assured that this drug demonstrated “in vitro” a strong higher potency compared to other antivirals against the virus and also with limited toxicity.
In two different animal models of infection by the coronavirus Sars-CoV-2, the test demonstrated the reduction of viral replication and a 99 percent decrease in viral loads was found in the lung of animals treated with plitidepsin.
The researchers noted in the Science publication that although toxicity is a concern in any antiviral targeting a human cell protein, the safety profile of plitidepsin is well established in humans and that the well-tolerated doses of this drug are have been used in the clinical trial against COVID-19 are even lower than those used in these experiments.
The publication concludes that plitidepsin works by blocking the aforementioned protein (eEF1A), which is present in human cells, and which is used by Sars-CoV-2 to reproduce and infect other cells. This mechanism culminates in antiviral efficacy also “in vivo”.
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“We believe that our data and the initial positive results from the PharmaMar clinical trial suggest that plitidepsin should be seriously considered to expand clinical trials for the treatment of COVID-19,” the researchers said.
The company recalls, in the same note released, that in the face of the continuing worldwide spread of the disease and the growing desperation to find a treatment, the director of the Institute for Quantitative Biosciences (QBI) at the University of California in San Francisco, Nevan Krogan, joined forces with researchers from the University of California, the Gladstone Institute, the Icahn School of Medicine at Mount Sinai, the Pasteur Institute, and the Howard Hughes Medical Institute, in the search for a treatment.
This group of researchers was the first to draw a comprehensive map of the covid-19 genome and to discover that the virus interacts with 332 proteins in human cells, the Spanish company stressed. Currently, the Spanish biopharmaceutical PharmaMar It is already negotiating with different regulatory bodies the start of the planned phase III trials.
EFE
