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Applied Biochemistry and Biotechnology

, Volume 185, Issue 3, pp 799–814 | Cite as

An “All-In-One” Pharmacophoric Architecture for the Discovery of Potential Broad-Spectrum Anti-Flavivirus Drugs

  • Nomagugu B. Ncube
  • Pritika Ramharack
  • Mahmoud E. S. Soliman
Article

Abstract

A precipitous increase in the number of flaviviral infections has been noted over the last 5 years. Despite these outbreaks, treatment protocols for infected individuals remain ambiguous. Numerous studies have identified NITD008 as a potent flavivirus inhibitor; however, clinical testing was dismissed due to undesirable toxic effects. The binding landscape of NITD008 in complex with five detrimental flaviviruses at the RNA-dependent RNA polymerase active sites was explored. An “all-in-one” pharmacophore model was created for the design of small molecules that may inhibit a broad spectrum of flaviviruses. This pharmacophore model approach serves as a robust cornerstone, thus assisting medicinal experts in the composition of multifunctional inhibitors that will eliminate cross-resistance and toxicity and enhance patient adherence.

Keywords

Flaviviridae Pharmacophore model Free-binding energy Binding landscape NITD008 RdRp 

Notes

Funding Information

The authors would like to thank the Centre of High Performance Computing in Cape Town (www.chpc.ac.za) for the computational facility and the National Research Foundation (NRF) of South Africa and the School of Health Sciences, UKZN, for the scholarships and financial support.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

12010_2017_2690_MOESM1_ESM.docx (18 kb)
ESM 1 (DOCX 17 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Nomagugu B. Ncube
    • 1
  • Pritika Ramharack
    • 1
  • Mahmoud E. S. Soliman
    • 1
  1. 1.Molecular Bio-Computation and Drug Design Laboratory, School of Health SciencesUniversity of KwaZulu-NatalDurbanSouth Africa

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