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The group of scientists, led by the Spanish virologist Adolfo García-Sastre, from the Sinai Hospital in New York, assures that plitidepsin is 100 times more potent than Remdesivir, the first antiviral to stop Covid-19, which until now has not shown overwhelming effectiveness.
A Plitidepsin is a synthetic drug based on a substance produced by a species of sea squirt from the Mediterranean Sea.: invertebrate and hermaphrodite animals that live anchored in stones. Pharmamar has developed a drug under the brand name Aplidine to treat multiple myeloma, a cancer that originates in the plasma cells of the bone marrow, which has only been approved in Australia for now.
After the start of the pandemic, The Spanish company Pharmamar has started clinical trials with the drug against Covid-19.
According to the company, the compound reduces viral load in hospitalized patients, however verified scientific data has yet to be published.
According to a study published in the journal Sciences, the García-Sastre team, in Together with experts from the University of California, San Francisco, the Pasteur Institute in Paris and the company Pharmamar, he has tracked down all the proteins of the new coronavirus that interact with human proteins. Then, they looked at known drugs that can interfere with these interactions and identified 47 promising drugs. Among them, plitidepsin, which appears to be one of the most promising. It is between nine and 85 times more effective at multiplying the virus than the other two drugs in the same group.
The treatments directed not against the virus, but against a specific protein of the patient, are more effective in the appearance of new variants.García-Sastre’s team launched another study, this only preliminary, in which it shows that these two treatments, Plitidepsin and Ralimetinib, another molecule used in the treatment of cancer, have a similar efficacy against the British variant of SARS- CoV-2. The same is true for Remdesivir, which targets the virus directly, but Plitidepsin is ten times more potent against the new coronavirus than Remdesivir.
The scientists compared the effects of plitidepsin with Remdesivir in two groups of mice infected with SARS-CoV-2. And the results show that plitidepsin reduces the duplication of the virus about 100 times more and also fights inflammation in the respiratory tract.
The molecule does not attack the virus directly, but rather a human protein needed to hijack the cells’ biological machine and use it to make thousands of copies of itself.
Plitidepsin blocks a human protein known as eEF1A, without which the virus’ replication machine cannot function.
“Our results and the positive data from Pharmamar’s clinical trials suggest that further clinical trials with plitidepsin for the treatment of Covid-19 should be prioritized.”conclude the study authors.
“The molecular mechanism that this drug targets is also important in the duplication of many other viruses, including influenza viruses and respiratory syncytial viruses,” explained García-Sastre. A long way to go
However, independent experts emphasize that there is still a long way to go. “This is an excellent preclinical study conducted by a group of very reliable researchers,” said Marcos López, president of the Spanish Society of Immunology.
Já Elena Muñez, researcher at the Puerta de Hierro Hospital in Madrid, states that “these results are very preliminary”.
“This type of preclinical data is carried out with experiments in totally controlled rats, a situation very different from what we experience with hospitalized patients,” he added in statements to the Spanish newspaper. The country.
For the CSIS virologist Isabel Sola, The study “is very promising because it provides us with a new treatment against infection.”
Isabel Sola’s team had conducted a previous study on the use of plitidepsin and found it to be effective in preventing the duplication of the influenza virus and SARS in 2002. One of the strengths of this new drug is its low toxicity in moderate doses. Information from studies conducted to measure the effect of plitidepsin against myeloma.
“The mechanism of action of this medicine is new. It can target the cells of the infected person and not the virus., it could be used together with Remdesivir, which is positive ”, comments Ana Fernández Cruz, infectious diseases assistant at Hospital Puerta de Hierro in Madrid.
Pharmamar is finalizing the official process to request a phase III clinical trial, in which the efficacy of the drug in hospitalized patients will be studied.
“This work confirms the powerful activity and high therapeutic index of plitidepsin and that, due to its special mechanism of action, it inhibits SARS-CoV-2 independently of the mutation in protein S, such as the variants in South Africa and Brazil or the new mutations that have recently appeared in Denmark ”, explained José María Fernández, President of Pharmamar.
“We are working with the pharmaceutical agencies to start the phase III trial that will be carried out in several countries,” he added.
