Neuraminidase and hamagglutinin were found to be the molecular targets in swine flu. Studies of these proteins were

Transcription

1 Available Online through ISSN: X CODEN: IJPTFI Research Article ANALYSIS OF ANTI-VIRAL COMPOUNDS ON THE PROTEIN MOLECULES WHICH CAUSE SWINE FLU OF H1N1 SUBTYPE Jayalakshmi. T* and Krishnamoorthy.P Dept. of Bioinformatics, Bharath University, Chennai, Tamil Nadu, India. Received on Accepted on Abstract Neuraminidase and hamagglutinin were found to be the molecular targets in swine flu. Studies of these proteins were done and structures were modelled by in silico method. Over amplification of these proteins inactivated by a number of antiviral properties holding compounds. Among these, zanamivir, quercetin and rimantidine molecular dynamics properties were analysed and docked with these targets to determine their binding energies. The aim of the present investigation is to predict the identified targets neuraminidase and hamagglutinin in swine flu, creating ligand library having antiviral perceiving molecules like catechin, flavanoids, alkaloids, saponin and also to determine ligand binding energies for the targets. Keywords: Neuraminidase, hamagglutinin, H1N1, Swine flu. Introduction Swine influenza is known to be caused by influenza a subtypes H1N1, H1N2, H3N1, H3N2, and H2N3.The most recent isolated influenza viruses from pigs have been H1N1 viruses. Swine flu viruses cause high levels of illness and low death rates in pigs. Swine influenza viruses may circulate among swine throughout the year. The classical swine flu virus (an influenza type A H1N1 virus) was first isolated from a pig in 1930.Like people, pigs can get influenza (flu), but swine flu viruses are not the same as human flu viruses. Swine flu viruses do not normally infect humans. However, sporadic human infections with swine flu have occurred in the past and have mainly affected people who had direct contact with pigs. But the current swine flu outbreak is different.the most worrying feature of the present outbreak is the swift human-to-human transmission of this virus.it is caused by a new swine flu virus that is happening among IJPT Jan-2013 Vol. 4 Issue No Page 5055

2 people who haven't had any contact with pigs. When the flu spreads from person-to-person, instead of from animals to humans, it can continue to mutate, making it harder to treat because people have no natural immunity. The virus spreads when an infected person coughs or sneezes around another person. People can become infected by touching something with the flu virus on it and then touching their mouth, nose or eyes. Swine influenza viruses are not transmitted by food. You cannot get swine influenza from eating pork or pork products. Eating properly handled and cooked pork and pork products are safe.cooking pork to an internal temperature of 160 F kills the swine flu virus as it does other bacteria and viruses. The symptoms of swine flu in people are expected to be similar to the symptoms of regular human seasonal influenza like: Fever, Lethargy, Running nose, Cough, Sore throat, Lack of appetite, Nausea and vomiting and Diarrhoea in some cases.to diagnose swine influenza A infection, a respiratory specimen would generally need to be collected within the first 4 to 5 days of illness (when an infected person is most likely to be shedding virus). Some patients, especially children, may shed virus for 10 days or longer. Materials and Methods Databases used: NCBI PDB GENECARD PIR PUBCHEM Tools used: ARGUS LAB PRODRG SERVER MOLEGRO VIRTUAL DOCKER YASARA. CORINA DATABASES: Genbank: Databank of genetic sequences operated by a division of the NATIONAL INSTITUTE OF HEALTH. IJPT Jan-2013 Vol. 4 Issue No Page 5056

3 Protein Data Bank: Jayalakshmi. T* et al. /International Journal Of Pharmacy & Technology A Protein Data Bank (PDB) is a database, which has a collection of protein structure. Genecard: Genecard is a database, which has collection of information about the genes. PIR and PUBCHEM: PIR is a Protein Information Resource database, here we can retrieve protein sequences in PIR format and PubChem is a database of chemical molecules. Docking Methods: Method which predicts the preferred orientation of one molecule to a second when bound to each other to form Corina tool: a stablecomplex. `CORINA will generate 3D coordinates for the given structure. A new page will be generated showing the 3D molecular model if you have RASMOL, CHIME, or some similar program installed on your computer). Corina is online tool used to convert the SMILE structures to 3D format. Its is available from the website 'Molecular Network'. The link to the tool is Results & Discussion Database, the targets NEURAMINIDASE & HAMAGGLUTININ details were taken to analyse. IJPT Jan-2013 Vol. 4 Issue No Page 5057

4 NCBI: GENE: IJPT Jan-2013 Vol. 4 Issue No Page 5058

5 Protein Structure H1N1: Neuraminidase: The structural information of NEURAMINIDASE & HAMAGGLUTININ was retrieved from Protein Data Bank as pdb coordinates. The pdb coordinates were saved to the local hard disk for future use. IJPT Jan-2013 Vol. 4 Issue No Page 5059

6 SIMULATORY ANALYSIS OF DOCKING PROCESS OF NEURAMINIDASE: NEURAMINIDASE AND QUERCETIN: The QUERCETIN was perfectly docked with NEURAMINIDASE. The binding properties of ligand with target are tabulated below: The ligand binding energy : The RMSD value : 0 The MolDockScore : IJPT Jan-2013 Vol. 4 Issue No Page 5060

7 Summary Jayalakshmi. T* et al. /International Journal Of Pharmacy & Technology Swine flu is a respiratory illness of pigs caused by infection with swine influenza a virus (SIV). While swine flu viruses normally do not infect humans, occasional infections of humans do occur. Human cases of swine influenza a virus infection occur in individuals who have had a history of recent direct contact with pigs or close (within 6 feet) contact with pigs. Rare instances of human-to-human transmission have been documented. Swine flu infections have also occurred in individuals with no history of exposure to pigs. Symptoms typically range from a mild respiratory illness to flu-like symptoms with fever. Treatment involves the use of antiviral medications begun as soon as possible after the onset of symptoms. Vaccines are available to be given to pigs to prevent swine flu in these animals. The swine flu pandemic of 2009 is caused by a novel influenza A (H1N1) virus that was originally referred to as "swine flu" because many of the genes in this new virus were very similar to influenza viruses that normally occur in pigs in North America. However, this new virus is actually quite different from the typical swine flu viruses found in pigs; the virus responsible for the Pandemic is termed H1N1 flu virus or novel H1N1 flu virus. This virus first caused illness in Mexico and the United States in March and April, H1N1 flu is spread from person to person, unlike typical swine flu as described above. In 2009 vaccines are being developed for the prevention of swine flu in humans.neuraminidase and Hamagglutinin gene was found to be the most important targets involved in Swine Flu. Over activation of this gene may lead to the differentiation of Swine Flu. Based on these data, the Neuraminidase is inhibited with the potential leads like allicin and alliin and the Hamagglutinin protein is inhibited with vinblastine and vincristine. Homology modeling was done to find the structure of Neuraminidase and it was docked with allicin and alliin and vinblastine and vincristine respectively. Conclusion: The study of the structural & functional properties of the targets Neuraminidase and Hamagglutinin was done by insilico method. These targets are responsible for the molecular pathogenetic state of Swine Flu. Inhibitors of Neuraminidase and Hamagglutinin such as QUERCETIN and RIMANTIDINE were found to be the best drug for antiviral activity of Swine Flu and can be used as effective anti- viral drugs after performing invitro experiments in IJPT Jan-2013 Vol. 4 Issue No Page 5061

8 future. Jayalakshmi. T* et al. /International Journal Of Pharmacy & Technology References 1. a b c d e f "Swine influenza". The Merck Veterinary Manual Retrieved April 30, Bouvier NM, Palese P "The biology of influenza viruses". Vaccine 26 Suppl 4: D PMID September Kimura H, Abiko C, Peng G, et al "Interspecies transmission of influenza C virus between humans and pigs". Virus Res. 48 (1): PMID April Matsuzaki Y, Sugawara K, Mizuta K, et al."antigenic and genetic characterization of influenza C viruses which caused two outbreaks in Yamagata City, Japan, in 1996 and 1998". J. Clin. Microbiol. 40 (2): PMID PMC: February Lynch JP, Walsh EE "Influenza: evolving strategies in treatment and prevention". Semin Respir Crit Care Med 28 (2): doi: /s PMID (April 2007). 6. a b c "Swine Influenza". Swine Diseases (Chest). Iowa State University College of Veterinary Medicine. 7. Ma W, Vincent AL, Gramer MR, Brockwell CB, Lager KM, Janke BH, Gauger PC, Patnayak DP, Webby RJ, Richt JA "Identification of H2N3 influenza A viruses from swine in the United States". Proc Nat Acad Sci USA 104 (52): doi: /pnas PMID PMC: (26 December 2007). 8. Shin JY, Song MS, Lee EH, Lee YM, Kim SY, Kim HK, Choi JK, Kim CJ, Webby RJ, Choi YK. "Isolation and characterization of novel H3N1 swine influenza viruses from pigs with respiratory diseases in Korea". Journal of Clinical Microbiology 44 (11): doi: /jcm PMID (2006). 9. Yassine HM, Al-Natour MQ, Lee CW, Saif YM. "Interspecies and intraspecies transmission of triple reassortant H3N2 influenza A viruses". Virol J 28 (4): 129. doi: / x PMID (November 2007). 10. Kilbourne, E. D., W. G. Laver, J. L. Schulman, and R. G. Webster.Antiviral activity of antiserum specific for an influenza virus neuraminidase.j. Virol. 2: (1968). Corresponding Author: Jayalakshmi. T* jayamaniraaja07@gmail.com IJPT Jan-2013 Vol. 4 Issue No Page 5062