Applied Biochemistry and Biotechnology

, Volume 187, Issue 1, pp 194–210 | Cite as

Exploring the Lead Compounds for Zika Virus NS2B-NS3 Protein: an e-Pharmacophore-Based Approach

  • K. Rohini
  • Pratika Agarwal
  • B. Preethi
  • V. Shanthi
  • K. RamanathanEmail author


The rapid spread of the Zika virus and its association with the abnormal brain development constitute a global health emergency. With a continuing spread of the mosquito vector, the exposure is expected to accelerate in the coming years. Despite number of efforts, there is still no proper vaccine or medicine to combat this virus. Of note, the NS2B-NS3 protein is proven to be the potential target for the Zika virus therapeutics. Hence, e-pharmacophore-based drug design strategy was employed to identify potent inhibitors of NS2B-NS3 protein from ASINEX database consisting of 467,802 molecules. A 3D e-pharmacophore model was generated using PHASE module of Schrödinger Suite. The generated model consists of one hydrogen bond acceptor (A), two hydrogen bond donors (D), and two aromatic rings (R), ADDRR. The model was further evaluated for its ability to screen actives using enrichment analysis. Subsequently, high-throughput virtual screening protocol was employed, and the resultant hit molecules were also examined for its binding free energies and ADME properties using Prime MM-GBSA and Qikprop module of Schrodinger packages, respectively. Finally, the screened hit molecule was subjected to molecular dynamics simulation to examine its stability. Overall, the results from our analysis suggest that compound BAS 19192837 could be a potent inhibitor for the NS2B-NS3 protein of the Zika virus. It is also noteworthy to mention that our results are in good agreement with literature evidences. We hope that this result is of immense importance in designing potential drug molecules to combat the spread of Zika virus in the near future.


Zika virus Virtual screening Enrichment analysis ASINEX database Prime MM-GBSA Molecular simulation 



The authors gratefully acknowledge Vellore Institute of Technology, Vellore for the support through Seed Grant for Research.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interests.


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Authors and Affiliations

  1. 1.Department of Biotechnology, School of Bio Sciences and TechnologyVellore Institute of TechnologyVelloreIndia

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