Introduction

This invention concerns the medical field and, in particular, the treatment of pathologies caused by RNA viruses, specifically by SARS-CoV-2, inhibiting the activity of RdRp polymerase (RNA dependent RNA polymerase), essential for virus replication in host cells and thus also blocking the resulting disease. In recent years, RdRp has emerged as an attractive target for the development of new antiviral drugs due to its high retention among distant evolutionary RNA viruses, the absence of RdRp homologs in mammalian cells, extensive knowledge of the structure and functions of RdRp and the easy development and subsequent availability of biochemical assays for rapid screening of large libraries of compounds.

Technical features

The present invention concerns compounds derived from 4-chromone by a general formula (Figure 1) and their medical use as RdRp polymerase inhibitors of SARS-cov-2 virus. Such formulations may be administered orally, nasally, subcutaneously, or intramuscularly. In particular, such formulations shall include one or more pharmaceutical excipients suitable depending on the route of administration. To obtain such compounds, a general procedure was described, consisting of 9 steps: 1. Aldolic condensation, 2. Oxidative cyclization, 3. Demethylation, 4. Alkylation of 3-hydroxy chromone, 5. Deprotetion of benzyl, 6. Alpha alkylation of esters, 7. Claisen condensation, 8. Dehydrating cyclization, 9. Ester hydrolysis. The activity of the invention compounds was tested experimentally by evaluating the enzymatic activity of RNA-dependent polymerase RNA (SARS-cov-2) using an enzyme test in vitro. TRL 2/3.

Possible Applications

• Medical use in the prevention and/or treatment of a disease caused by an RNA virus such as Hepatitis C virus (HCV), Ebola virus and Zika virus.

Advantages

• Small molecules, which can be easily synthesized
• The main structure and substructures define scaffolds that allow good chemical diversity, allowing the investigation of many compounds with similar structure
• The activity of the described compounds is not limited to SARS-cov-2 virus only, but also includes other RNA viruses
• Scope of drug repurposing, thus speeding up the evaluation of activity and toxicity of a possible drug for the new pathology detected