Structure Analysis of Interacting Domains of RNA Dependent RNA Polymerase (Rdrp) Complex in Nipah Virus

Abstract

Nipah virus is an emerging zoonotic paramyxovirus that is responsible for severe outbreaks in humans and livestocks. This negative stranded RNA virus carries RNA-dependent RNA polymerase (RdRp) complex which is required for viral RNA replication and transcription as a catalytic subunit of viral replicase. We have investigated the 3D structures of four domains from three proteins- Nucleocapsid (N), Phosphoprotein (P) and Polymerase (L) which contribute to form RdRp complex. The presence of intrinsic disorder regions in those proteins under native condition which made the in vitro study of structure difficult. In our study, the 3D homology models of the domain Alpha MoRE and PXD (forming N-P complex), and domain PMD and Domain I (forming P-L complex) were generated and evaluated. Protein-protein docking studies of these four domains was performed which elucidated the structural aspects of RdRp complex and also showed the nature of individual interaction (N-P and P-L). The evidence of the weak binding of Alpha MoRE with PXD than the binding affinity of PMD to Domain I have suggested that, the Alpha MoRE-PXD interaction as a valuable drug target.