A more effective drug against COVID-19?

The pandemic caused by SARS-CoV-2 is the result of zoonotic transmission, that is, from animal to man. This type of transmission risks being at the origin of more and more epidemics since human activities tend to promote close contact with animal reservoirs. The current crisis is itself a symptom of other future problems. It is therefore necessary to develop new treatments, not only for COVID-19, but also for other infectious pathologies.

The 2 drugs available at the moment are Remdesvir and Dexamethasone, both of which have limited effectiveness. Plitidepsine is a drug that is used against certain myelomas and is currently undergoing clinical trials for use against COVID-19. Plitidepsine has an inhibiting effect on SARS-CoV-2 replication, 27 times more powerful that Remdesivir in in vitro tests. What’s more, Plitidepsine has limited toxic effects on cells, different to those caused by Remdesivir. So one may be able to complement the other in a combined treatment programme, particularly since their joint use may reduce respective toxicity.

How does this new drug work? Plitidepsine inhibits the activity of cellular eEF1A, which plays a role in the traductional cellular machinery enabling the production of proteins. When infection takes place, this cellular machinery is hijacked and used to produce viral proteins that allow the formation of new virions. Inhibiting cellular eEF1A therefore allows the manufacture of viral proteins to be reduced, so slowing the virus’ multiplication. It has been shown in vitro that this enables a reduction in viral RNA replication and the production of viral proteins.

This drug has been tested in vivo  on 2 types of mouse susceptible to SARS-CoV-2 infection, and also showed a reduction in virus replication and a lessening of lung inflammation. These results show that Plitidepsine can be envisaged as a treatment against COVID-19, and the drug is currently undergoing human clinical trials.