Publication Abstract from PubMed
Coronaviruses (CoVs) cause numerous diseases, including Middle East respiratory syndrome and severe acute respiratory syndrome, generating significant health-related and economic consequences. CoVs encode the nucleocapsid (N) protein, a major structural protein that plays multiple roles in the virus replication cycle and forms a ribonucleoprotein complex with the viral RNA through the N protein's N-terminal domain (N-NTD). Using human CoV-OC43 (HCoV-OC43) as a model for CoV, we present the 3D structure of HCoV-OC43 N-NTD complexed with ribonucleoside 5'-monophosphates to identify a distinct ribonucleotide-binding pocket. By targeting this pocket, we identified and developed a new coronavirus N protein inhibitor, N-(6-oxo-5,6-dihydrophenanthridin-2-yl)(N,N-dimethylamino)acetamide hydrochloride (PJ34), using virtual screening; this inhibitor reduced the N protein's RNA-binding affinity and hindered viral replication. We also determined the crystal structure of the N-NTD-PJ34 complex. On the basis of these findings, we propose guidelines for developing new N protein-based antiviral agents that target CoVs.
Structural basis for the identification of the N-terminal domain of coronavirus nucleocapsid protein as an antiviral target.,Lin SY, Liu CL, Chang YM, Zhao J, Perlman S, Hou MH J Med Chem. 2014 Mar 27;57(6):2247-57. doi: 10.1021/jm500089r. Epub 2014 Mar 12. PMID:24564608[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
