Identifying chemicals with potential therapy of HIV based on protein-protein and protein-chemical interaction network

PLoS One. 2013 Jun 6;8(6):e65207. doi: 10.1371/journal.pone.0065207. Print 2013.

Abstract

Acquired immune deficiency syndrome (AIDS) is a severe infectious disease that causes a large number of deaths every year. Traditional anti-AIDS drugs directly targeting the HIV-1 encoded enzymes including reverse transcriptase (RT), protease (PR) and integrase (IN) usually suffer from drug resistance after a period of treatment and serious side effects. In recent years, the emergence of numerous useful information of protein-protein interactions (PPI) in the HIV life cycle and related inhibitors makes PPI a new way for antiviral drug intervention. In this study, we identified 26 core human proteins involved in PPI between HIV-1 and host, that have great potential for HIV therapy. In addition, 280 chemicals that interact with three HIV drugs targeting human proteins can also interact with these 26 core proteins. All these indicate that our method as presented in this paper is quite promising. The method may become a useful tool, or at least plays a complementary role to the existing method, for identifying novel anti-HIV drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / analogs & derivatives
  • 1-Deoxynojirimycin / chemistry
  • 1-Deoxynojirimycin / pharmacology
  • Algorithms*
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology
  • CCR5 Receptor Antagonists
  • Computer Simulation
  • Cyclohexanes / chemistry
  • Cyclohexanes / pharmacology
  • Databases, Chemical
  • Didanosine / chemistry
  • Didanosine / pharmacology
  • Drug Design
  • Drug Discovery
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / metabolism
  • Host-Pathogen Interactions
  • Humans
  • Maraviroc
  • Models, Molecular
  • Protein Interaction Mapping*
  • Protein Interaction Maps*
  • Receptors, CCR5 / chemistry
  • Receptors, CCR5 / metabolism
  • Triazoles / chemistry
  • Triazoles / pharmacology

Substances

  • Anti-HIV Agents
  • CCR5 Receptor Antagonists
  • Cyclohexanes
  • Receptors, CCR5
  • Triazoles
  • 1-Deoxynojirimycin
  • miglustat
  • Didanosine
  • Maraviroc

Grants and funding

This work was supported by grants from National Basic Research Program of China (2011CB510102, 2011CB510101), Innovation Program of Shanghai Municipal Education Commission (12ZZ087), National Natural Science Foundation of China (Grant 81001399) and the grant of “The First-class Discipline of Universities in Shanghai”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.