Functional and structural studies of the SARS-CoV-2 accessory protein Nsp8 for novel antiviral therapies

The lack of therapies for COVID-19 calls for detailed studies of the life cycle of SARS-CoV-2, the disease's causative agent. Recent studies have revealed how the virus could reshape the host cell and interact with cellular proteins for optimal replication. Intriguingly, an essential viral accessory protein Nsp8 interacts with LARP7 and MePCE proteins that play important gene regulatory roles in human cells, potentially explaining how the virus rewires the cells and hides from our immune system. We will use multi-disciplinary approaches to shed a light on this important biology of SARS-CoV-2. We shall also solve the three-dimensional structure of Nsp8 bound to LARP7, and identify compounds that interfere with this interaction. In conclusion, our studies shall reveal how SARS-CoV-2 manipulates human cells for its own benefit. Moreover, they shall yield compounds blocking viral replication, paving the way to the urgently needed COVID-19 therapeutics.