Finding candidate drugs for hepatitis C based on chemical-chemical and chemical-protein interactions

PLoS One. 2014 Sep 16;9(9):e107767. doi: 10.1371/journal.pone.0107767. eCollection 2014.

Abstract

Hepatitis C virus (HCV) is an infectious virus that can cause serious illnesses. Only a few drugs have been reported to effectively treat hepatitis C. To have greater diversity in drug choice and better treatment options, it is necessary to develop more drugs to treat the infection. However, it is time-consuming and expensive to discover candidate drugs using experimental methods, and computational methods may complement experimental approaches as a preliminary filtering process. This type of approach was proposed by using known chemical-chemical interactions to extract interactive compounds with three known drug compounds of HCV, and the probabilities of these drug compounds being able to treat hepatitis C were calculated using chemical-protein interactions between the interactive compounds and HCV target genes. Moreover, the randomization test and expectation-maximization (EM) algorithm were both employed to exclude false discoveries. Analysis of the selected compounds, including acyclovir and ganciclovir, indicated that some of these compounds had potential to treat the HCV. Hopefully, this proposed method could provide new insights into the discovery of candidate drugs for the treatment of HCV and other diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Antiviral Agents / metabolism*
  • Antiviral Agents / pharmacology*
  • Computational Biology / methods
  • Drug Discovery*
  • Gene Expression Regulation, Viral / drug effects
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Humans

Substances

  • Antiviral Agents

Grants and funding

This study was supported by the National Basic Research Program of China (2011CB510101, 2011CB510102), the National Natural Science Foundation of China (61202021, 31170952, 31371335, 61373028, 11371008, 61203240), the Innovation Program of the Shanghai Municipal Education Commission (12YZ120, 12ZZ087, 14YZ102), the Shanghai Educational Development Foundation (12CG55), the Shanghai Municipal Natural Science Foundation (13ZR1455600) and the Science & Technology Program of the Shanghai Maritime University (No. 20120105, No. 20120109). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.