Abstract We present in this work a first X‐ray Absorption Spectroscopy study of the interactions of Zn with human BST2/tetherin and SARS‐CoV‐2 orf7a proteins as well as with some of their complexes. The analysis of the XANES region of the measured spectra shows that Zn binds to BST2, as well as to orf7a, thus resulting in the formation of BST2‐orf7a complexes. This structural information confirms the the conjecture, recently put forward by some of the present Authors, according to which the accessory orf7a (and possibly also orf8) viral protein are capable of interfering with the BST2 antiviral activity. Our explanation for this behavior is that, when BST2 gets in contact with Zn bound to the orf7a Cys 15 ligand, it has the ability of displacing the metal owing to the creation of a new disulfide bridge across the two proteins. The formation of this BST2‐orf7a complex destabilizes BST2 dimerization, thus impairing the antiviral activity of the latter. Think zinc ! We conjecture that in the case of SARS‐CoV‐2, the orf7a accessory protein acts as a BST2 antagonist. We provide evidence, based on sequence analysis, Molecular Dynamics simulations as well as XAS experiments, that Zn ions play a key role in the SARS‐CoV‐2 virus strategy to escape the immune response mediated by the BST2 host protein.
【저자키워드】 SARS-CoV-2, orf7a protein, Tetherin/BST2, XANES, Zn speciation, 【초록키워드】 immune response, Dynamics, Proteins, antiviral activity, SARS‐CoV‐2, Protein, Sequence analysis, information, Evidence, Ligand, Interaction, Analysis, Contact, Spectroscopy, Viral protein, complex, host protein, SARS‐CoV‐2 virus, Absorption, BST2, bind, resulting, complexes, experiments, Ion, destabilize, impairing, 【제목키워드】 SARS‐CoV‐2,