Drug repurposing and new antivirals

New, efficient, broad-spectrum antivirals are needed to combat viruses that cause disease in plants, animals and humans. In future decades, the next occurrence of a new RNA virus epidemic or pandemic is unpredictable. Therefore, there is an essential need for developing new broad-spectrum antiviral drugs which could be administered in multiple drug therapies. In 1963, idoxuridine was approved as the first antiviral drug. Since then, many antiviral drugs have been developed for clinical use to treat millions of humans worldwide. How antiviral agents are used is based on previous knowledge of 1) how the virus interacts with its target cell, 2) how it replicates, and 3) which viral components are recognized by the immune response of the host. The goal of this project is to select non-toxic molecules that have been already used to treat other pathologies and to study whether they can be repurposed as broad spectrum antivirals. With a combination of virology, cell biology, biochemistry and microscopy methods, we are currently characterizing several compounds with antiviral properties against pathogenic RNA viruses. An alternative to viral-targeted drugs should be the development of new drugs directed to host proteins that are usurped during infection to support viral replication. One of the advantages of this approach is avoiding the emergence of drug resistance.We are currently testing the inhibition of key cellular proteins involved in lipid transport and mitochondrial dynamics, and studying their effect on the viral replication cycle. This strategy may lead to new antivirals against a variety of RNA viruses, as these cellular pathways are commonly exploited by many different viruses.

García-Serradilla & Risco. Virus Research 2021; Fernández-Oliva, Ortega-González & Risco. Cellular Microbiology 2019; García-Serradilla, Risco & Pacheco. Virus Research 2019.