Periodic Reporting for period 1 - FINDER (FINDER: FIghtiNg DEngue viRus, a novel strategy for the development of fully protective antiviralsthat act by disrupting the DENV NS3/NS5 interaction)
Okres sprawozdawczy: 2018-05-01 do 2020-04-30
The identification of molecules able to block specific and critical viral targets would clearly have an enormous impact on society. Indeed, antiviral drugs would dramatically decrease the global disease burden of dengue by essentially preventing the deadly complications and reducing the mortality rate of DENV infections. As a consequence, the availability of effective therapeutic options for DENV would also have a profound economic benefit as it will help to reduce the huge economic losses due to the costs incurred for hospitalisation and supportive care, mostly in low/middle-income countries.
This project is focused on the early stages of the drug development and the main objective of FINDER is the development of innovative and effective anti-DENV therapeutic options able to disrupt the interaction between the viral NS3 and NS5 proteins, which play a key role in the viral replication. Since this target is highly conserved among the different DENV serotypes, the inhibition of this interaction by small molecules may represent a promising strategy for the development of drugs with efficacy against all DENV. Moreover, this class of compounds could be less prone to induce resistance as increasing evidence suggests that dissociative inhibitors of protein-protein interactions possess a high barrier to drug resistance. Overall, this project led to the identification of antiviral compounds acting by disrupting the NS3-NS5 interaction, paving the way for the development of a new class of selective anti-DENV agents.
The results of this project, avoiding any confidential information, were extensively communicated at the most prestigious international conferences in the field of antiviral drug research and through academic seminars and several outreach activities. Considering the lack of available antiviral agents against DENV, the identification of potential preclinical drug candidates has a clear and attractive commercial potential, and we are currently exploring the possibility of protecting the new intellectual properties (IP) generated during the project. Finally, these results will be published in peer-reviewed, open access journals.
For this reason, the IP generated throughout this project are expected to be protected and could potentially lead to industrial exploitation. Finally, new techniques (i.e. in vitro and cell-based assays), protocols and data were established and they will continue to be widely disseminated among the scientific community, making useful tools and information available not only for antiviral compound discovery but also for studying DENV biology.