Description and purpose
The DEFENCE project aims to develop new broad-spectrum antivirals for the treatment of circulating coronaviruses, potentially extendable to new variants and other virus families. To this end, research will focus on both viral helicases (SARS-CoV-2 nsp13) and cellular helicases (DDX3X), which are strategically important targets for viral replication.

Purpose
DEFENCE aims to generate innovative antiviral candidates through iterative cycles of molecular modeling, chemical synthesis, and biological validation. The goal is to identify and optimize compounds active on viral and cellular helicases, fostering a multidisciplinary approach to better understand virus-host interactions and generate innovative molecular tools capable of blocking viral replication in vitro.
Expected results
The project aims to identify at least one antiviral candidate with broad-spectrum activity suitable for future preclinical studies, define new chemical classes active on nsp13 and DDX3X and produce advanced knowledge on helicases as therapeutic targets, laying the foundations for “first-in-class” drugs.
Achieved results
Several series of molecules were designed and synthesized as potential reversible, covalent, and allosteric inhibitors of the cellular and viral helicases targeted by the project. Screening of isolated proteins identified several chemical classes of inhibitors. Subsequent screening of cells infected with SARS-CoV-2 and other potentially pandemic viruses identified promising broad-spectrum antivirals.