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Pharmaceutical Research

, 36:27 | Cite as

High Throughput and Computational Repurposing for Neglected Diseases

  • Helen W. HernandezEmail author
  • Melinda Soeung
  • Kimberley M. Zorn
  • Norah Ashoura
  • Melina Mottin
  • Carolina Horta Andrade
  • Conor R. Caffrey
  • Jair Lage de Siqueira-Neto
  • Sean EkinsEmail author
Expert Review

Abstract

Purpose

Neglected tropical diseases (NTDs) represent are a heterogeneous group of communicable diseases that are found within the poorest populations of the world. There are 23 NTDs that have been prioritized by the World Health Organization, which are endemic in 149 countries and affect more than 1.4 billion people, costing these developing economies billions of dollars annually. The NTDs result from four different causative pathogens: protozoa, bacteria, helminth and virus. The majority of the diseases lack effective treatments. Therefore, new therapeutics for NTDs are desperately needed.

Methods

We describe various high throughput screening and computational approaches that have been performed in recent years. We have collated the molecules identified in these studies and calculated molecular properties.

Results

Numerous global repurposing efforts have yielded some promising compounds for various neglected tropical diseases. These compounds when analyzed as one would expect appear drug-like. Several large datasets are also now in the public domain and this enables machine learning models to be constructed that then facilitate the discovery of new molecules for these pathogens.

Conclusions

In the space of a few years many groups have either performed experimental or computational repurposing high throughput screens against neglected diseases. These have identified compounds which in many cases are already approved drugs. Such approaches perhaps offer a more efficient way to develop treatments which are generally not a focus for global pharmaceutical companies because of the economics or the lack of a viable market. Other diseases could perhaps benefit from these repurposing approaches.

KEY WORDS

dengue ebola echinococcosis elephantiasis high throughput screening kinetoplastids lymphatic filariasis neglected tropical diseases onchocerciasis repurposing schistosoma zika 

Notes

Acknowledgments and Disclosures

This work was supported by Award Numbers 1R43GM122196-01 and R44GM122196-02A1 “Centralized assay datasets for modelling support of small drug discovery organizations” from NIH/ NIGMS. 1UH2TR002084-01 “Repurposing pyronaridine as a treatment for Chagas disease” from NIH/ NCATS 1R21TR001718-01 “Repurposing pyronaridine as a treatment for the Ebola virus” from NIH / NCATS. MM thanks the support of the Brazilian CNPq/FAPEG DCR (grant 300508/2017-4). We are very grateful for our many collaborators and colleagues who contributed to the various efforts referenced herein. HWH is a Managing Member of KAL Research Initiatives, LLC. KMZ is an employee and SE is an employee and owner of Collaborations Pharmaceuticals, Inc.

Supplementary material

11095_2018_2558_MOESM1_ESM.docx (89 kb)
ESM 1 (DOCX 88 kb)
11095_2018_2558_MOESM2_ESM.sdf (2.6 mb)
ESM 2 (SDF 2684 kb)

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Copyright information

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

Authors and Affiliations

  1. 1.KAL Research Initiatives LLCHoustonUSA
  2. 2.MD Anderson Cancer CenterUniversity of TexasHoustonUSA
  3. 3.Collaborations Pharmaceuticals Inc.RaleighUSA
  4. 4.University of Texas at AustinAustinUSA
  5. 5.LabMol - Laboratory for Molecular Modeling and Drug Design Faculdade de FarmaciaUniversidade Federal de Goias – UFGGoiâniaBrazil
  6. 6.Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical SciencesUniversity of California San DiegoSan DiegoUSA

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