• Prasanthi Polamreddy Centre for Nanoscience and Nanotechnology, International Research Centre, Sathyabama Institute of Science and Technology, Jeppiaar Nagar, Rajiv Gandhi Salai, Chennai 600119, India Excelra Knowledge Solutions Pvt Ltd, NSL-SEZ, Uppal, Hyderabad 500039, India
  • Vinita Vishwakarma Centre for Nanoscience and Nanotechnology, Sathyabama University, Chennai- 600 119, India
  • Manoj Kumar Mahto Excelra Knowledge Solutions Pvt Ltd, NSL-SEZ, Uppal, Hyderabad – 500039, India


Objective: The objective of the current study was to elucidate the 3D pharmacophoric features of benzothiadiazine derivatives that are crucial for inhibiting Hepatitis C virus (HCV) Non-structural protein 5B (NS5B) and quantifying the features by building an atom based 3D quantitative structure-activity relationship (3D QSAR) model.

Methods: Generation of QSAR model was carried out using PHASE 3.3.

Results: A five-point pharmacophore model with two hydrogen bond acceptors, one negative ionization potential and two aromatic rings (AANRR) was found to be common among a maximum number of benzothiadiazine based NS5B inhibitors. A statistically significant 3D QSAR model was obtained from AANRR.6 which had correlation-coefficient (R2) value of 0.924, cross-validated correlation-coefficient (Q2) of 0.774, high Fisher ratio of 138 and low root mean square standard error (RMSE=0.29). There is another parameter, Pearson's R, its value emphasizes correlation between predicted and observed activities of the test set. For the current model, Pearson's R-value is 0.90, hence underlining the good quality of the model. The present study suggests that nitrogen atom of benzothiadiazine sulfamide ring, oxyacetamide group attached to C7 carbon of benzothiadiazine and sulfonamide oxygens are crucial for NS5B inhibitory activity. Prediction of activities of hit drugs generated in earlier research suggests that Aprepitant (Phase predicted activity: 6.9) could be a potential NS5B inhibitor.

Conclusion: This 3D QSAR model developed was statistically good and can be used to predict the activities of newly designed NS5B inhibitors and virtual screening as well. Predict the activities of newly designed NS5B inhibitors and virtual screening as well.

Keywords: Pharmacophore, QSAR, NS5B, HCV, Benzothiadiazine, Inhibitor


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How to Cite
Polamreddy, P., V. Vishwakarma, and M. K. Mahto. “COMBINATORIAL PHARMACOPHORE MODELING AND ATOM BASED 3D QSAR STUDIES OF BENZOTHIADIAZINES AS HCV-NS5B INHIBITORS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 10, no. 3, Mar. 2018, pp. 43-69, doi:10.22159/ijpps.2018v10i3.23734.
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