An “Old” Protein with A New Story: Coronavirus Endoribonuclease Is Important for Evading Host Antiviral Defenses

Deng, Xufang; Baker, Susan C

Here we review the evolving story of the coronavirus endoribonuclease (EndoU). Coronavirus EndoU is encoded within the sequence of nonstructural protein (nsp) 15, which was initially identified as a component of the viral replication complex. Biochemical and structural studies revealed the enzymatic nature of nsp15/EndoU, which was postulated to be essential for the unique replication cycle of viruses in the order Nidovirales. However, the role of nsp15 in coronavirus replication was enigmatic as EndoU-deficient coronaviruses were viable and replicated to near wild-type virus levels in fibroblast cells. A breakthrough in our understanding of the role of EndoU was revealed in recent studies, which showed that EndoU mediates the evasion of viral double-stranded RNA recognition by host sensors in macrophages. This new discovery of nsp15/EndoU function leads to new opportunities for investigating how a viral EndoU contributes to pathogenesis and exploiting this enzyme for therapeutics and vaccine design against pathogenic coronaviruses.