In-vivo proof-of-concept of a broad-spectrum antiviral (2018 PROD 00089) coordinated by Juana Diez

There is an urgent need to develop efficient treatments against some of the most virulent emerging viruses such as Chikungunya virus (CHIKV), Dengue virus (DENV), West-Nile virus (WNV) and Zika virus (ZKV). The World Health Organization (WHO) is concerned about the speed with which these infections spread throughout the world and points out that they will eventually become a global health problem. Moreover, all these viruses produce acute infections and it is of paramount importance to treat them early after the onset of the symptoms for drugs to be effective. However, an early diagnosis of these infections still remains as an unsolved challenge due to the fact that there are no accurate serological tests and all of these viruses are spread through identical geographical areas, share the same mosquito vectors and produce similar initial symptoms. Consequently, the ideal solution to treat these infections is a broad-spectrum antiviral that can be administered before reaching a final diagnosis.

Our objective is to develop circular RNAs (circRNAs) with the potential to inactivate functional regions of multiple viral RNA genomes, with the final goal of developing broad-spectrum antivirals against the emerging viruses CHIKV, DENV, WNV and ZIKV. These broad-spectrum antivirals (i) could be administered before an accurate diagnosis, dramatically increasing the likelihood of viral control and (ii) will enormously reduce the cost and time required to develop specific drugs and vaccines. The novel use of circRNAs to develop antiviral therapies have fundamental advantages over other approaches, including greater stability than other compounds, resistance to the emergence and selection of escaping mutants and extreme versatility, since the technology can be very simply optimized to treat other diseases. As an initial proof-of-concept we have designed circRNAs to inhibit hepatitis C virus (HCV) infection in human hepatoma cell lines by targeting different essential regions in the HCV genome.

The overall goal of this project is test whether circRNAs with broad spectrum activities against emerging infections in cell culture are also effective in vivo using mice model. After a series of preliminary in-vitro and in-vivo assays, our final task is to perform a pharmacodynamic study in mice infected with the corresponding viruses. The positive results of this pharmacodynamics study will serve as a validation of the behaviour of the technology in a relevant environment and will become an essential part of the draft technical data package that will be used to outline the protocols for the Phase 1 clinical testing in human individuals.

This project has been co-financed by the European Union through the European Regional Development Fund (FEDER) and is supported by the Secretary of Universities and Research of the Department of Business and Knowledge of the Generalitat de Catalunya.