Structural, biophysical and biochemical elucidation of the SARS-CoV-2 nonstructural protein 3 macro domain.

The pandemic outbreak of a novel coronavirus, SARS-CoV-2, has threatened the global public health and economy since late December 2019. SARS-CoV-2 encodes the conserved macro domain within non-structural protein 3, which may reverse cellular ADP-ribosylation and potentially cut the signal of a viral infection in the cell. Herein, we report that the SARS-CoV-2 macro domain was examined as a poly-ADPR binding module and possessing mono-ADPR cleavage enzyme activity. After confirming the ADPR binding ability via a biophysical approach, the X-ray crystal structure of the SARS-CoV-2 macro domain was determined and structurally compared with those of other viruses. This study provides structural, biophysical, and biochemical bases to further evaluate the role of the SARS-CoV-2 macro domain in the host response via ADP-ribose binding but also as a potential target for drug design against COVID-19.