Structural bioinformatics strategy in the design of antiviral drugs from natural products
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Abstract
Structural bioinformatics has emerged as a powerful tool to approach the development of structure based drug design (SBDD) due to the availability of vast experimental data generated from X-ray crystallography and NMR spectroscop. These experimental data are important in elucidating atomic details of ligand-target complex. However, in some cases, the structures obtained through these experiments cannot be used directly in SBDD because of significant changes between apo and ligand-bound forms. To overcome this limitation and gain additional insight into the motions occuring during ligand-binding, molecular dynamics simulation is frequently utlised as it allows an improved conformational space sampling.
In this talk, I will underline recent advances in the methodologies as well as their application to influenza (1) and dengue (2) antiviral design. I will also highlight some of our works that applied these methods in our quest to better understand how chemical modifications in a series of ligands synthesised from Malaysian natural product scaffolds bring about changes in their binding affinities (structure-activity relationships). From this understanding, we discovered compounds from cinnamic acid as well as lawsone scaffolds which possessed potential antiviral activities at submicromolar concentrations (3 & 4).
References
- Yusuf, M.; Mohamed, N.; Mohamad, S.; Janezic, D.; Damodaran, K. V.; Wahab, H. A., H274Y's Effect on Oseltamivir Resistance: What Happens Before the Drug Enters the Binding Site. J Chem Inf Model 2016, 56, 82-100.
- Yotmanee, P.; Rungrotmongkol, T.; Wichapong, K.; Choi, S. B.; Wahab, H. A.; Kungwan, N.; Hannongbua, S., Binding specificity of polypeptide substrates in NS2B/NS3pro serine protease of dengue virus type 2: A molecular dynamics Study. J Mol Graph Model 2015, 60, 24-33.
- Hariono, M.; Abdullah, N.; Damodaran, K. V.; Kamarulzaman, E. E.; Mohamed, N.; Hassan, S. S.; Shamsuddin, S.; Wahab, H. A., Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay. Sci Rep 2016, 6, 38692.
- Sharma, G.; Kumar, S. V.; Wahab, H. A., Molecular docking, synthesis, and biological evaluation of naphthoquinone as potential novel scaffold for H5N1 neuraminidase inhibition. J Biomol Struct Dyn 2016, 1-25.
About the speaker
Professor Habibah A. Wahab is Dean of the School of Pharmaceutical Sciences at the Universiti Sains Malaysia (USM — University of Science, Malaysia).
- Laboratory of Biocrystallography and Structural Bioinformatics (which became the Center for Chemical Biology)
- Laboratory of Pharmaceutical Design and Simulation
- Centre for Hits-to-Lead
- Malaysian Institute of Pharmaceutical and Nutraceuticals
- USM-RIKEN Laboratory for Bioprobe Discovery with Professor Hiroyuki Osada, from Japanese research institute RIKEN.
In 2014, Habibah was appointed as an associate editor for the Journal of Chemical Information and Modeling by the American Chemical Society, a position she has held until recently.
During her career, she has accepted the following visiting academic positions:
- Visiting Professorship in Universite Henri Poincare, France
- Visiting Professorship in Chulalongkorn University, Thailand
- Visiting Lecturer in Osaka University, Japan
- Visiting Lecturer in Padjadjaran University, Indonesia
- Visiting Scientist in Department of Chemistry, Penn State University, U.S.A.
- JSPS Scholar in Osaka University, Japan.
She also formerly served as the Deputy Chair of the Steering Committee of the Pacific Rim Grid Application and Middleware Assembly (PRAGMA).
Administratively, Habibah has been seconded to Malaysia's Ministry of Science, Technology and Innovation two times: first in 2007 as Director of the Advanced Drug Delivery Centre; and in 2012 as the Director General, and later in 2014, Executive Director, of the Malaysian Institute of Pharmaceuticals and Nutraceuticals, Ministry of Science, Technology and Innovation.
In 2010, Habibah was promoted to a full professorship at USM.