The journal Science has published an article confirming that its compound called plitidepsin has “powerful preclinical efficacy” against COVID-19.
An in vitro and in vivo study by a team of scientists in New York, San Francisco, and Paris showed that this compound leads to a reduction in viral replication, resulting in a 99% reduction in viral loads in the lungs. of animals treated with plitidepsin , according to the researchers in their article published in the journal Science.
The researchers determine that “the antiviral activity of plitidepsin against SARS-CoV-2 is produced through the inhibition of a known target ( eEF1A) ” and assure that this drug has demonstrated strong antiviral potency “in vitro”, in comparison with other antivirals against SARS-CoV-2, and also with limited toxicity.
“We believe that our data and the initial positive results from the clinical trial suggest that plitidepsin should be seriously considered for expanded clinical trials for the treatment of COVID-19,” the authors explain.
The compound, already authorized in some markets to treat tumors, blocks a protein associated with the SARS-CoV-2 virus. The pharmaceutical company that has developed the potent antiviral said it is already in talks with various regulatory agencies to begin Phase III trials.
If the compound plitidepsin is successful in treating COVID-19, the virus will not be able to become resistant to treatment through mutations, something that is currently of great concern with the current spread of variants such as the South African or the United Kingdom.
Coping with the pandemic
COVID-19 is a virus-induced inflammatory disease of the airways and lungs with multi-organ involvement that can cause severe respiratory and systemic problems. Replication of SARS-CoV-2 in the lungs leads to inflammatory, innate, and adaptive immune responses that cause significant damage to host tissue. In the terminal stage it can lead to a lung disease that, for now, has limited treatment options and a poor prognosis.
It is currently treated with oxygen therapy and ventilation , along with the antiviral remdesivir and the anti-inflammatory dexamethasone. Remdesivir and dexamethasone have certainly improved patient outcomes in clinical trials and have been approved for emergency use by regulatory agencies, but their efficacy is limited and they do not hinder viral replication. This leaves a continuing need for the development or reuse of antiviral drugs for the treatment of COVID-19.
“In our animal experiments, we detected a slight loss of body weight in mice that were treated with plitidepsin daily , while mice that received a single dose of 1 mg / kg did not lose weight and still showed reductions in viral lung titers. . It is unclear whether this observed toxicity is mouse specific, and although toxicity is a concern with any host-directed antiviral, the safety profile of plitidepsin is well established in humans. Additionally, the dose of plitidepsin used in an ongoing COVID-19 clinical trial is significantly lower than that used in these experiments and has been well tolerated in patients with minimal side effects. This study establishes that plitidepsin is an anti-SARS-CoV-2 agent targeting the host with efficacy in vivo, ”the researchers write.
Referencia: Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A Science 25 Jan 2021: DOI: 10.1126/science.abf4058
