Project description

During the last two decades, several coronaviruses (CoV) outbreaks have caused high pathogenicity and mortality rates in humans. In particular, COVID-19 pandemic caused by SARS-CoV-2 is causing an increasing death toll and paralyzing the world economy. This highlights the importance of anti-CoV drugs and vaccines. Although COVID-19 vaccines are being developed to prevent infection, there is no effective therapy available to cure COVID-19 patients. Replication is a fundamental aspect of viral life cycle and is orchestrated by viral proteins. As it is central for virus survival, viral proteins involved in replication are highly conserved and not impacted by mutations causing zoonosis.

The goal of this project is to identify small molecules that specifically target a highly conserved interaction between two CoV proteins, which we recently showed to be vital for CoV replication. We will establish an in vitro miniaturized assay to assess interaction between these two proteins, and use it to screen compound libraries. Hits will be tested in infection models against beta-coronaviruses, including SARS-CoV-2. We expect to identify therapeutic leads for both the current and future COVID outbreaks.

Short bio

My research interests concern the degradative pathway of autophagy, and they focus on (1) The regulation and mechanism of autophagy, and (2) autophagy in disease (viral infections and neurodegeneration). We have generated unique electron microscopy procedures to integrate ultrastructural analyses into our investigations. This technology, plus our overall expertise in autophagy but also membrane traffic and organelle biogenesis, has permitted us to realize numerous collaborative studies to solve pressing biological questions.