Pharmacophore Modelling Analysis and Synthesis of Vanillin Derivatives as Neuraminidase Inhibitors of Influenza Virus and 3CLpro Inhibitors of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)

Woon Yi, Law (2020) Pharmacophore Modelling Analysis and Synthesis of Vanillin Derivatives as Neuraminidase Inhibitors of Influenza Virus and 3CLpro Inhibitors of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV). Masters thesis, Universiti Malaysia Sarawak.

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Abstract

Influenza remain as global threat and public health concern over the years. For the past century, there were a number of significant influenza pandemics recorded, which were H1N1 Spanish flu (1918), the H2N2 Asian flu (1957), the H3N2 Hong Kong flu (1968), and the H1N1 swine flu (2009). Despite the fact that licensed drugs were available, antigenic drifts and shifts of influenza virus resulted in mutation of the virus, therefore the virus possess resistance towards available drugs. Thus, research in discovering more effective drugs or inhibitors against influenza virus is continuously necessary. Focus is given particularly to the discovery of neuraminidase inhibitors (NAIs) of influenza virus due to the important role of neuraminidase in facilitating the spread of virus. At the same time, severe acute respiratory syndrome coronavirus (SARS-CoV) also remain as a global threat due to the high rate of mutation and recombination. There were no licensed drugs available for SARS-CoV despite the numerous research being conducted, hence discovery of potent drugs or inhibitors for SARS-CoV become necessarily important. Focus is given particularly to the finding of 3CLpro inhibitors of SARS-CoV for the importance of 3CLpro in viral polyproteins processing and replicase complex activity controlling. Vanillin was reported in research for its biological activities, whereby the most important activity is the antiviral activity against NA. Research related to vanillin as NAIs are very potential and interesting, but considerably limited. Therefore, in this research, a list of Schiff base vanillin derivatives were evaluated and analysed for their potential as NAIs and 3CLpro inhibitors via computer-aided drug design (CADD), particularly ligand-based pharmacophore modelling, virtual screening and structure-based molecular docking. As a result, 7 out of 9 vanillin derivatives, labelled as A1 to A7, were concluded to possess potential as both NAIs and 3CLpro inhibitors. The 7 vanillin derivatives successfully synthesized and characterized by Fourier Transform-Infrared spectroscopy (FT-IR).

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