Lin, M.-H.M.-H.LinChang, S.-C.S.-C.ChangChiu, Y.-C.Y.-C.ChiuJiang, B.-C.B.-C.JiangWu, T.-H.T.-H.WuCHUN-HUA HSU2021-05-182021-05-182020https://www.scopus.com/inward/record.url?eid=2-s2.0-85096151656&partnerID=40&md5=b2b361807a02a8a1f80b9886856227aahttps://scholars.lib.ntu.edu.tw/handle/123456789/561290The pandemic outbreak of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has threatened the global public health and economy since late December 2019. SARS-CoV-2 encodes the conserved macro domain within nonstructural 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-ADP-ribose (ADPR) binding module and possessed 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. ? 2020 ACS. All rights reserved.ADP-ribose; COVID-19; crystal structure; macro domain; SARS-CoV-2[SDGs]SDG3nonstructural protein 3; poly(adenosine diphosphate ribose); adenosine diphosphate ribose; antivirus agent; viral protein; adenosine diphosphate ribosylation; Article; circular dichroism; conformational transition; controlled study; crystal structure; dissociation constant; enthalpy; entropy; enzyme activity; human; hydrogen bond; isothermal titration calorimetry; ligand binding; nonhuman; priority journal; protein binding; protein structure; Severe acute respiratory syndrome coronavirus 2; stoichiometry; X ray; Betacoronavirus; chemistry; Coronavirus infection; drug design; metabolism; pandemic; protein conformation; protein domain; virology; virus pneumonia; Adenosine Diphosphate Ribose; Antiviral Agents; Betacoronavirus; Coronavirus Infections; Drug Design; Humans; Pandemics; Pneumonia, Viral; Protein Conformation; Protein Domains; Viral Nonstructural Proteinsjournal article10.1021/acsinfecdis.0c00441329462242-s2.0-85096151656