Characterization of the NiRAN domain from RNA-dependent RNA polymerase provides insights into a potential therapeutic target against SARS-CoV-2
Fig 1
The CoV-2-RdRp NiRAN domain presents a kinase/phosphotransferase like structural organisation.
(A) The NiRAN and the interface domains of the CoV-2-RdRp present an arrow head like structure (helices in royal blue, strands in peach and loops in green). (B) The overall topology of the NiRAN (brown background, helices as marked as H and strands are marked as S) and interface domain (grey background, helices as marked as h and strands are marked as s) along with β-hairpin structure (brick red background, strands are marked as B). (C) The NiRAN domain possess a topology (left panel) that borrows elements from the canonical kinase fold (centre panel) as well as the non-canonical kinase fold of TgBPK1 (right panel). (D-I) The structural superimpositions of the secondary structural elements of CoV-2-RdRp NiRAN with known kinases reveal significant alignment in the antiparallel β-sheet and in the helices that follow. (D) Lim 2 kinase domain. (E) Syk kinase domain (F) O-mannosyl kinase domain. (G) IRAK4 kinase domain. (H) FGFR2 kinase domain. (I) Insulin receptor kinase domain (The aforementioned kinases’ structural elements are shown in cyan, CoV-2-RdRp NiRAN structural elements shown in yellow).