Several structural approaches are currentlyongoing by our group at CNR-IBB, in order to understand the mechanism of viralinfection by SARS-CoV-2 [1-3]. These combine molecular biology withcomputational studies, structural studies, and protein-protein interactionstudies.

Mechanistically, SARS-CoV-2 enters the cellthrough the binding of the Spike protein to the ACE2 receptors, as previouslyobserved for SARS-CoV. Given the available structural information on theinteractions between the Spike protein and the human ACE2 receptor, wedeveloped a panel of Spike interactors aiming to bind SARS-CoV-2 Spike protein withhigh affinity [2], for both therapeutic and diagnostic purposes.

Other important aspects of viral life whichare under investigation in our group relate to mechanisms of viral hijackingthe host cell metabolic machinery to take advantage for their replication. Incollaboration with CNR-IGM, key actors of SARS-CoV-2 replication machinery arebeing studied with a two-fold aim: (i) for a better understanding of theirmechanisms and for the development of inhibitors [2] and (ii) to investigatetheir interaction modes with important host factors, like the DDX helicases[3].