SARS-CoV-2 orf7a and orf8 proteins and their Zn-mediated interaction with BST2

The most supported hypothesis for the orf7a function is the interference with virion budding operated by cellular antigens, while the orf8 function is still unknown. We aim at studying the interaction of orf7a and orf8 with the bone marrow stromal antigen 2 (BST2). BST2 dimerization and oligomerization involve intermolecular disulfide bonds between cysteine residues and are strongly influenced by the presence of divalent cations, such as Zn2+. We want to test the hypothesis [7] that the orf7a and orf8 proteins have been selected to counteract BST2 antiviral activity by bringing in situ Zn2+ cations owing to the presence of multiple Zn-finger domains. The formation of orf7a/BST2 and orf8/BST2 complexes assisted by the presence of Zn2+ may enable the virus to evade the antiviral activity of BST2. In this proposal we aim at determining the Zn2+coordination mode in orf7a, orf8 and BST2 to check the possible formation of orf7a/BST2 and orf8/BST2 complexes.