Large-scale structure-activity relationship study of hepatitis C virus NS5B polymerase inhibition using SMILES-based descriptors

Apilak Worachartcheewan, Virapong Prachayasittikul, Alla P. Toropova, Andrey A. Toropov, Chanin Nantasenamat

Research output: Contribution to journalArticle

Abstract

Hepatitis C virus (HCV) is composed of structural and non-structural proteins involved in viral transcription and propagation. In particular, NS5B is an RNA-dependent RNA polymerase for viral transcription and genome replication and is a target for designing anti-viral agents. In this study, classification and quantitative structure-activity relationship (QSAR) models of HCV NS5B inhibitors were constructed using the Correlation and Logic software. Molecular descriptors for a set of 970 HCV NS5B inhibitors were encoded using the simplified molecular input line entry system notation, and predictive models were built via the Monte Carlo method. The QSAR models provided acceptable correlation coefficients of R^{2}R2 and Q^{2}Q2 in the ranges of 0.6038–0.7344 and 0.6171–0.7294, respectively, while the classification models displayed sensitivity, specificity, and accuracy in ranges of 88.24–98.84, 83.87–93.94, and 86.50–94.41 %, respectively. Furthermore, molecular fragments as substructures involved in increased and decreased inhibitory activities were explored. The results provide information on QSAR and classification models for high-throughput screening and mechanistic insights into the inhibitory activity of HCV NS5B polymerase.

Original languageEnglish
Pages (from-to)955-964
Number of pages10
JournalMolecular Diversity
Volume19
Issue number4
DOIs
Publication statusPublished - Nov 1 2015

Fingerprint

hepatitis
viruses
Structure-Activity Relationship
Viruses
Hepacivirus
Quantitative Structure-Activity Relationship
Transcription
RNA
inhibitors
Antiviral agents
RNA Replicase
Monte Carlo Method
Viral Genome
genome
substructures
Software
entry
correlation coefficients
logic
Monte Carlo method

Keywords

  • Data mining
  • HCV NS5B polymerase inhibitors
  • Hepatitis C virus
  • Monte Carlo method
  • Structure-activity relationship

ASJC Scopus subject areas

  • Organic Chemistry
  • Catalysis
  • Inorganic Chemistry
  • Physical and Theoretical Chemistry
  • Information Systems
  • Drug Discovery
  • Molecular Biology

Cite this

Large-scale structure-activity relationship study of hepatitis C virus NS5B polymerase inhibition using SMILES-based descriptors. / Worachartcheewan, Apilak; Prachayasittikul, Virapong; Toropova, Alla P.; Toropov, Andrey A.; Nantasenamat, Chanin.

In: Molecular Diversity, Vol. 19, No. 4, 01.11.2015, p. 955-964.

Research output: Contribution to journalArticle

Worachartcheewan, A, Prachayasittikul, V, Toropova, AP, Toropov, AA & Nantasenamat, C 2015, 'Large-scale structure-activity relationship study of hepatitis C virus NS5B polymerase inhibition using SMILES-based descriptors', Molecular Diversity, vol. 19, no. 4, pp. 955-964. https://doi.org/10.1007/s11030-015-9614-2
Worachartcheewan, Apilak ; Prachayasittikul, Virapong ; Toropova, Alla P. ; Toropov, Andrey A. ; Nantasenamat, Chanin. / Large-scale structure-activity relationship study of hepatitis C virus NS5B polymerase inhibition using SMILES-based descriptors. In: Molecular Diversity. 2015 ; Vol. 19, No. 4. pp. 955-964.
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