COVID-19: they show how the drug plitidepsin inhibits the reproduction of SARS-CoV-2

A study co-led by the Spanish IrsiCaixa and the Higher Council for Scientific Research (CSIC) shows how the drug aplidin (plitidepsin) acts to inhibit the replication of SARS-CoV-2 within cells: it prevents the formation of cellular compartments where it is replicates virus material.

In this way, it interferes with the cells and prevents the progression of the viral infection, explains the CSIC in a statement, noting that “its operation reinforces its potential to combat future variants of SARS-CoV-2, since this replication step of the virus is common to all variants of the virus.

The study, in the review phase and reported by the CSIC, was presented last Wednesday at the Conference on Retroviruses and Opportunistic Infections in Barcelona (northeast Spain).

For the CSIC, the drug plitidepsin is one of those that has shown “greatest efficacy” in blocking the replication of SARS-CoV-2 in laboratory experiments.

“When we launched this study to analyze the antiviral activity of plitidepsin in the cell, we did not expect to discover that its target of action was in such an initial stage of replication of SARS-CoV-2”, explains Cristina Risco.

Risco is a researcher at the Spanish National Center for Biotechnology and co-leader of the study together with scientists from the IrsiCaixa AIDS Research Institute, the Animal Health Research Center and PharmaMar -which produces the drug-.

This would block a host cell molecule that is necessary for SARS-CoV-2 to form the vesicles where new viruses are made.

Unlike the vast majority of antivirals, plitidepsin – which is in a phase III clinical trial – acts on the host cell and not on the virus, blocking essential processes shared between the different variants of SARS-CoV-2.

“This fact makes it a potential tool to combat not only the current SARS-CoV-2, but also future variants that may emerge,” says the same source.

The team demonstrated, in cell cultures in the laboratory, that low amounts of plitidepsin are capable of inhibiting, 48 hours after SARS-CoV-2 infection, the ability of the virus to replicate.

“Through electron microscopy techniques, we have been able to see how, in the presence of the drug, the double-membrane vesicles, which are the cellular compartments in which the genetic material of SARS-CoV-2 replicates, do not form,” details Martin Sachse, a researcher at the Spanish CNB-CSIC and the Carlos III Health Institute.

“We think that this is due to the fact that the non-structural proteins of the virus necessary for the creation of these vesicles do not form as a consequence of the action of the drug”, he argues.

The team also used immunostaining techniques: “We can confirm that plitidepsin acts at a very early point in the viral infection cycle, specifically at the moment when the genetic material of SARS-CoV-2 sends orders for the viral proteins to be produced. they will form the compartments where viruses replicate their genetic material and direct the synthesis of new viruses”, adds Nuria Izquierdo-Useros, from IrsiCaixa.