Synthesis of broad-spectrum antiviral compounds in a GLP-like laboratory

Outbreaks of viral infections have been a high burden to human society, both in the past and in the present, with the catastrophic toll of COVID-19 pandemic not yet behind the corner. In the last years, the availability of effective antiviral drugs has been an utmost priority to tackle emerging viruses, such as Dengue virus, West Nile virus and Japanese Encephalitis virus which still remain untreated due to lack of valid therapeutic options. However, the development of new treatments to overcome this urgent need cannot come at the expense of quality.Currently, in the realm of life sciences, the development of safe and effective pharmaceuticals can only be possible if rigorous quality standards and regulations ensure the reliability and integrity of the research data. Despite its high scientific level, research in the academic world is still far from the level of accuracy and standardization which conversely is ubiquitous in the industry world. The lack of a robust quality system ensuring data integrity and reliability in academia enhances the gap between academic and industrial research, resulting in the former being less attractive for investors, not up to date with the constantly evolving scientific industry requirements, and thus hard to be externally recognized and valued. Good Laboratory Practice (GLP) is a framework aimed at promoting data reliability, reproducibility and integrity, and thus quality of scientific non-clinical research. The first part of this thesis focuses on the synthesis of two broad-spectrum antiviral compounds in a GLP-like laboratory, to be used as references for ADME assays, antiviral assays and in vivo protocols of certified quality, as part of TUSCAVIR.net project. “TUSCAVIR.net” stands for Tuscany Antiviral Research Network, and is aimed at creating a multidisciplinary, highly integrated and qualified network of laboratories from the Universities of Siena and Florence and the Universities Hospitals of Siena and Pisa for the discovery and development of novel antiviral drugs, entirely based in Tuscany. To provide an in vivo proof-of- concept, a topic gel formulation of one of the two reference antiviral compounds was setup in order to perform an efficacy test on a murine model of Herpes Simplex Virus-2 (HSV-2) vaginal infection. Our formulation was able to extend life expectancy and reduce the number of viral lesions in HSV-2 infected mice.