QSAR Studies on Thiazole Derivatives as HCV NS5A Inhibitors via CoMFA and CoMSIA Methods

Author(s): Jiayu Li, Wenyue Tian, Diaohui Gao, Yuying Li, Yiqun Chang, Jun Xu, Junxia Zheng*, Pinghua Sun*.

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 4 , 2019

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Graphical Abstract:


Background: Hepatitis C Virus (HCV) infection is the major cause of hepatitis after transfusion. And HCV Nonstructural Protein 5A (NS5A) inhibitors have become a new hotspot in the study of HCV inhibitors due to their strong antiviral activity, rapid speed of viral removing and broad antiviral spectrum.

Methods: Forty-five NS5A inhibitors were chosen to process three-dimensional quantitative structure- activity relationship (3D-QSAR) by using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. A training set consisting of 30 compounds was applied to establish the models and a test set consisting of 15 compounds was applied to do the external validation.

Results: The CoMFA model predicted a q2 value of 0.607 and an r2 value of 0.934. And the CoMSIA model predicted a q2 value of 0.516 and an r2 value of 0.960 established on the effects of steric, electrostatic, hydrophobic and hydrogen-bond acceptor. 0.713 and 0.939 were the predictive correlation co-efficients (r2pred) of CoMFA and CoMSIA models, respectively.

Conclusion: These conclusions provide a theoretical basis for drug design and screening of HCV NS5A complex inhibitors.

Keywords: 3D-QSAR, thiazole derivatives, HCV, NS5A inhibitors, broad antiviral spectrum, strong antiviral activity.

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Article Details

Year: 2019
Page: [453 - 460]
Pages: 8
DOI: 10.2174/1570180815666180702153529
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