Synthesis and activity evaluation of new anti-SARS-CoV2 compounds

The coronavirus impacted everyone’s life since it started in December 2019, by stopping all non-essential activities. This crown-virus, likely originated from bats, has spread through humans using its Spike protein as a key to enter the cells and replicate itself. This trimeric bulbous protein constitutes the main antigen against which the body can make antibodies. Knowing that, all pharmaceutical industries have created vaccines, all administrating the Spike protein either via a mRNA or viral vector vaccine. However, other types of medications are currently under investigation. A new molecule showing antiviral properties against COVID-19 has been discovered by Professor Soumillion’s group : the lactavir. This cyclic compound has shown inhibition of SARS-CoV-2 infection and syncytia formation, both crucially implicated in the development of severe cases. The goal of this project is to optimize the synthesis pathway leading to lactavir, in order to synthesize a deuterated version, which will allow biological studies and isotope tracking. In parallel, the first clues on the interaction between the lactam function and different human cell lines have been investigated. Those experiments were achieved with fluorescent compounds containing a lactavir derivative. The synthesis optimisation of lactavir was performed in two steps, starting from commercially available compounds. The cyclisation of the intermediary species was optimized and a deuterated version was obtained. The biological assays with fluorescent derivatives showed labelling on the three cell lines tested, with a preference for the macrophage THP-1 line. Protein electrophoresis showed covalent labelling of proteins. Further investigations still need to be made to find which proteins are modified by this compound.