Protein Modeling and Docking of Curcurin Against Neuraminidase, Hemagglutinin Proteins of Pandemic Influenza H1N1/2009

A new approach to anti-viral therapy in recent years has been relying on the modeling and docking processes in the quest of novel inhibitors. Curcurin, an ribosome-inactivating protein, from Jatropha curcas Linn. (Euphorbiaceae), a herbal plant that has been used in traditional folk medicine in many tropical countries, was investigated against 2 proteins of Pandemic Influenza H1N1/2009. Although the structural properties of curcin are well documented in the literature, the modeling and docking studies by in-silico techniques with phytoproteins are limited. In this pursuit, the modeling of Curcurin was carried out by Phyre2 and docking with Influenza virus proteins by using Hex, Patchdock and FireDock server. Further, we applied the Molecular operating environment (MOE) to analyze the protein interactions between Curcin and Hemagglutinin and with Neuraminidase. The present work provides the structural insight into the binding mode of curcin protein and forms the basis for designing future inhibitors of Influenza proteins. Keywoprds: Pandemic Influenza H1N1/2009, Curcurin, Protein Modeling, Docking. INTRODUCTION: Jatropha (Euphorbiaceae) is a genus of approximately 175 succulent plants, shrubs and trees (some are deciduous like Jatropha curcas L.). Irrespective of the species, extracts from different parts such as leaves, stem, bark and roots of the Jatropha plant have been used in ethno-medicines for a long time [1]. In the past two decades, study on the utilization of Jatropha oil (non-edible) as a feedstock for biofuel has gained a momentum, resulting in industrial scale cultivation. Apart from the seed oil, genus Jatropha is also a rich source of phytochemicals that can be utilized in agricultural, nutritional and pharmaceutical industries [2]. The toxicity of the whole seed from Jatropha curcas has been known for a long time. Its toxicity has been attributed to a protein component. A toxic protein was isolated from the seeds of Jatrophacurcas by Felke (1914), and was designated as “curcin” by him. He proposed that the curcin was a kind of toxalbumin [3], Barbieri (1993) reported the curcin was type I RIP, a single chain protein [4]. Many plants contain proteins that are capable of inactivating ribosome and accordingly are called ribosomeinactivating protein (RIP). Interests in RIP, particularly in Type I RIP have been growing since they are used as components of ‘immunotoxins’, one type of hybrid molecules consisting of a toxic peptide chain linked to an antibody [5]. Immunotoxins will be promisingly used to eliminate such targets as harmful cell, neoplastic, immunocompetent and parasitic cells. Traditionally, RIPs are recognized to deadenylate the large ribosomal RNA with high site specificity and inactivate the ribosomes owing to their RNA N-glycosidase activity [68]. The potential of some of the RIPs to depurinate the rRNA at multiple sites [9] along with several other polynucleotide substrates [10] has been addressed. Broad and diverse pharmacological attributes have been associated with RIPs, as protein synthesis-inhibitory, immunosuppressive, anti-tumor, antiviral, anti-HIV and abortificient traits to mention a few [11]. Phytomolecules have long served a pivotal role as potent active components towards strengthening and widening the pharmaceutical options against various ailments. Influenza is a respiratory infection caused by the influenza virus, which is transmitted mainly through airborne aerosols of respiratory secretions and direct or indirect Rahul Chavan et al /J. Pharm. Sci. & Res. Vol. 7(2), 2015, 70-75