Structural and binding characterization of the antiviral host Proteins, VIPERIN and VAPC

Abstract

Cellular proteins with antiviral properties have always been the priority area for researchers. Recent advances in the structural characterization of the proteins have provided a strong foundation towards these efforts. Human immune system act strongly against viral infection by up-regulation of certain proteins which are active against such infections. The present work is about two such cellular proteins, Viperin and VAPC, which show antiviral properties. Research work done in past decade proves the antiviral activities against whole range of viruses ranging from DNA virus to RNA virus. But these studies lack structural and biochemical details about viperin. My Ph.D. thesis work showed for the first time that viperin is a radical SAM domain protein and it was done by systematic removal of N- terminal domain and reconstitution of purified protein under anaerobic conditions. Another cellular protein, VAP inhibits HCV virus by interaction with HCV unstructured protein NS5B. Our results indicate that VAPC is a member of intrinsically unstructured protein (IUP) with no secondary and tertiary structures. Extensive NMR characterization reveals that the C-terminal half of VAPC is involved in binding with NS5B. The results demonstrate that the intrinsically unstructured VAPC form a ¿fuzz¿ complex with NS5B and also for the first time we designed a shorter VAPC-peptide which specifically bind NS5B with a Kd of 49.13 µM. In the future, functional characterization needs to be done to evaluate its potential as peptide mimic in treatment against HCV infection.