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Identification of potential Zika virus NS2B-NS3 protease inhibitors via docking, molecular dynamics and consensus scoring-based virtual screening

  • Lucy R. Bowen
  • Dennis J. Li
  • Derek T. Nola
  • Marc O. Anderson
  • Michael Heying
  • Adam T. Groves
  • Scott EagonEmail author
Original Paper

Abstract

The Zika virus has recently become a subject of acute interest after the discovery of the link between viral infection and microcephaly in infants. Though a number of treatments are under active investigation, there are currently no approved treatments for the disease. To address this critical need, we screened more than 7 million compounds targeting the NS2B-NS3 protease in an attempt to identify promising inhibitor candidates. Starting with commercially and freely available compounds, we identified six hits utilizing an exhaustive consensus screening protocol, followed by molecular dynamics simulation and binding energy estimation using MM/GBSA and MM/PBSA methods. These compounds feature a variety of cores and functionalities, and all are predicted to have good pharmacokinetic profiles, making them promising candidates for screening assays.

Graphical abstract

Virtual screen of potential Zika virus NS2B-NS3 protease inhibitors

Keywords

Docking Zika Molecular dynamics Consensus scoring Virtual screen 

Notes

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interests

The authors declare no conflicts of interest.

Supplementary material

894_2019_4076_MOESM1_ESM.docx (488 kb)
ESM 1 (DOCX 487 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Lucy R. Bowen
    • 1
  • Dennis J. Li
    • 1
  • Derek T. Nola
    • 1
  • Marc O. Anderson
    • 2
  • Michael Heying
    • 1
  • Adam T. Groves
    • 1
  • Scott Eagon
    • 1
    Email author
  1. 1.California Polytechnic State UniversitySan Luis ObispoUSA
  2. 2.San Francisco State UniversitySan FranciscoUSA

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