Title

Authors

Affiliation

¹Department of Biotechnology, Madhav Institute of Technology and Science, Race Course Road, Gola Ka Mandir, Gwalior (M.P.) India; ²Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai-400076; ³Apex Bioinformatics Centre, Department of Biotechnology, Ministry of Science and Technology, Lodhi Road, New Delhi – 110 003, India.

Email

gulshan@dbt.nic.in; *Corresponding author

Article Type

Hypothesis

Date

Received December 11, 2012; Revised December 21, 2012; Accepted December 22, 2012; Published January 09, 2012

4-hydroxypanduratin A is a secondary metabolite of Boesenbergia pandurata Schult. (Fingerroot) plant with various pharmacological activities such as neuroprotective, potent antioxidant, antibacterial and antifungal. Flaviviral NS2B/NS3 protease activity is essential for polyprotein processing and viral replication for Japanese Encephalitis Virus (JEV), a major cause of Acute Encephaltis in Asia. Inhibition of formation of this complex by arresting the binding of NS2B with NS3 would reduce the enzyme’s activity to meager proportions and hence would prevent further viral proliferation. The automated 3D structure of NS2B protein of the JEV GP78 was predicted based on the sequence-to-structure-to-function paradigm using I-TASSER and the function of NS2B protein was inferred by matching to other known proteins. The stereochemical quality of predicted structure was checked by PROCHECK. The antiviral activity of 4-hydroxypanduratin A against NS2B protein as a potential drug has been elucidated in this paper. Docking simulation analysis showed 4-hydroxypanduratin A as potential inhibitor of NS2B protein/cofactor which is necessary for NS3 protease activity. 220 derivatives of 4-hydroxypanduratin A were virtually screened with rigid criteria of Lipinski’s rule of 5 using Autodock4.2. 4-hydroxypanduratin A was found interacting with target hydrophilic domain in NS2B protein by two H-bonds (Gly80 and Asp81) with active residues, several hydrophobic interactions, Log P value of 5.6, inhibition constant (Ki) of 51.07nM and lowest binding energy of -9.95Kcal/Mol. Hence, 4-hydroxypanduratin A targeted to Site 2 will have sufficient profound effect to inhibit protease activity to abrogate viral replication. It could be a promising potential drug candidate for JEV infections using NS2B Site 2 as a Drug target.

Keywords

NS2B/NS3 protease, Japanese Encephalitis Virus, Structure prediction, I-TASSER, Molecular Docking, 4-hydroxypanduratin A.

Citation

Seniya et al. Bioinformation 9(1): 054-060 (2013)
 

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.