Research conducted by the University of Bari in collaboration with the Campus Bio-Medico University of Rome
The studies carried out by the research team of the University of Bari in collaboration with the Campus Bio-Medico University of Rome, formed by Luigi Leonardo Palese, Anna Maria Sardanelli, and Camilla Isgrò of the Department of Basic Medical Sciences, Neuroscience and Sense organs led to the identification of compounds active against SARS-CoV-2 responsible for COVID-19, capable of inhibiting an enzyme necessary for viral replication using the “drug repurposing” strategy.
This consists in the search for molecules already approved for some therapeutic indications that are also effective in another pathology of interest, in this case the SARS-CoV-2 infection. This approach of therapeutic repositioning of drugs, “drug repurposing”, when is successful, it allows to identify molecules immediately usable for the treatment of a pathology, with a considerable saving on research and development time and costs.
The research team focused on a particular SARS-CoV-2 enzyme, the so-called main protease. Technically it is a cysteine protease, from the type of amino acid that is functionally important in the cleavage mechanism operated by the enzyme on target proteins. This protease makes specific cuts on some viral proteins, cuts that are necessary for the functional maturation of these. Blocking this protease makes it impossible for the virus to complete its normal life cycle, thus stopping its replication.
2111 drugs were considered by in silico analysis for their ability to inhibit the activity of this enzyme. The most promising were experimentally analyzed in the laboratories of the Campus Bio-Medico University of Rome to evaluate their inhibitory activity on the purified viral enzyme. These analyzes led to the identification of ethacrynic acid as a promising inhibitor of the SARS-CoV-2 protease. It is a potent diuretic approved for clinical use in the treatment of hypertension and edema from heart, liver and kidney failure. The next step will be to clinically evaluate its efficacy and safety in the treatment of COVID-19.