An updated evolutionary study of Flaviviridae NS3 helicase and NS5 RNA-dependent RNA polymerase reveals novel invariable motifs as potential pharmacological targets

Mol Biosyst. 2016 Jun 21;12(7):2080-93. doi: 10.1039/c5mb00706b.

Abstract

The rate of Flaviviridae family virus infections worldwide has increased dramatically in the last few years. In addition, infections caused by arthropod vector viruses including Hepatitis C, West Nile, Dengue fever, Yellow fever and Japanese encephalitis are emerging throughout the world. Based on a recent taxon update, the Flaviviridae family comprises four main genera; Flavivirus, Hepacivirus, Pestivirus and a recent genus Pegivirus. Although the new scientific classification plays a key role in providing useful information about the relationships between viruses, many new documented viruses remain unclassified. Furthermore, based on the different results of several studies the classification is unclear. In an effort to provide more insights into the classification of viruses, a holistic evolutionary study of the two viral enzymes NS3 helicase and NS5 RNA-dependent RNA polymerase (RdRp) has been conducted in this study. These two viral enzymes are very crucial for the inhibition of viruses due to the fact that they are involved in the survival, proliferation and transmission of viruses. The main goal of this study is the presentation of two novel updated phylogenetic trees of the enzymes NS3 helicase and NS5 RdRp as a reliable phylogeny "map" to correlate the information of the closely related viruses and identify new possible targets for the Flaviviridae family virus inhibition. Despite the earliest trials for drugs against Flaviviridae related viruses, no antiviral drug vaccine has been available to date. Therefore there is an urgent need for research towards the development of efficient antiviral agents.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Antiviral Agents / pharmacology
  • Conserved Sequence
  • Databases, Genetic
  • Flaviviridae / drug effects
  • Flaviviridae / enzymology
  • Flaviviridae / genetics*
  • Models, Molecular
  • Phylogeny
  • Protein Conformation
  • Protein Interaction Domains and Motifs*
  • RNA Helicases / antagonists & inhibitors
  • RNA Helicases / chemistry
  • RNA Helicases / genetics
  • Sequence Analysis, DNA
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / genetics
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / genetics*

Substances

  • Antiviral Agents
  • NS3 protein, flavivirus
  • NS5 protein, flavivirus
  • Viral Nonstructural Proteins
  • Serine Endopeptidases
  • RNA Helicases