MOLECULAR INTERACTIONS BETWEEN NIPAH VIRUS V AND DNA DAMAGE-BINDING PROTEIN (DDB1): A COMPUTATIONAL MOLECULAR DOCKING STUDY

Abstract

Intro: The Nipah virus (NiV) V protein has been associated with evasion of host cell interferon (IFN) signal transduction, which promotes STAT degradation by binding to DNA damage-binding protein 1 (DDB1). Recent studies have shown that the NiV V protein was able to interact with DDB1 by its zinc finger domain (ZnFD) at C-terminal region (CTD). Methods: In this study, the molecular interactions between the NiV V proteins from two NiV isolates (NiV pig isolate, iP-V and NiV bat isolate, iB-V) and DDB1 protein were examined using computational molecular docking studies. Findings: The iP-V was noted to have a lower binding affinity (-13.2kcal/mol) and a total stabilization energy of -344.23kJ/mol toward DDB1 compared to iB-V, which has a binding affinity of -13.7kcal/mol and stabilization energy of -450.83kJ/mol. The iP-V interacted with DDB1 at amino acid residue positions 366 to 456, which involved both the NTD and CTD of V protein; while the interaction of iB-V with DDB1 was identified at the NTD only, at positions 2 to 172. There were two mutations identified in the CTD of iB-V, which is the zinc binding domain; therefore, it lacks one zinc ion in its ZnFD for interaction with DDB1. Nevertheless, the interaction of iP-V and iB-V with DDB1 involved three conserved residues on DDB1 (Tyr906, Arg928, and Phe1003). Additionally, the iP- V and iB-V bind to the beta-propeller A (BPA), beta-propeller C (BPC), and CTD of DDB1. Conclusion: The findings from this study demonstrated that the binding region of iB-V to DDB1 was different from that of iP-V due to the lack of one ZnFD in iB- V. Future studies such as site-directed mutagenesis of key amino acid residues will be needed to further confirm the interaction profile.