The global prevalence of the H1N1 infection in 2009 had made the World Health Organization to declare it a pandemic. Even though the occurrence is still continuing, it is not that severe as it was earlier. Similar to the seasonal flu, it has the potential to cause more significant health issues in certain group of people. The best strategy to avoid such flues is to get vaccinated every year. Molecular docking plays a vital role among the various drug designing strategies that are being used in computer-assisted drug designing. In this research, we have tested the molecular docking of Peramivir and Zanamivir on the Receptor Binding proteins of H1N1 Influenza Virus. The objective of the study was to review the efficacy of these neuraminidase inhibitors which are recently granted an Emergency Use Food and Drug Administration (FDA) for the treatment of  H1N1influenza in selected patients. Molecular docking is one of the foremost applied methods in structure-based drug design (SBDD) owing to its large level of accuracy and ability to confirm the small-molecule ligands within the acceptable target binding site. Molecular docking has evolved as an important tool for new drugs today. Molecular docking methods produce quantitative indications of binding energies, as well as ranges of docked molecules that support the binding affinity of ligand-receptor complexes with pharmacokinetic features. The reported binding energies are the sum of the total intermolecular energy, total internal energy, and torsional free energy excluding the energy of the unbound system. This method was used to determine the potential interactions between the receptor and the ligand, as well as the length of the bond. Docked orientations were recorded at the completion of each run, and the resulting molecules were analyzed for geometry and the number of hydrogen bonds. Thus, docking study of two compounds was performed, and both compounds demonstrated higher binding energy. Peramivir has a binding energy of -5.03, whereas zanamivir has a binding energy of -3.88. The results presented in the current study provide data that are useful for the future treatment of H1N1 infection.

References

1. Kuntz?Simon, G., & Madec, F. (2009). Genetic and antigenic evolution of swine influenza viruses in Europe and evaluation of their zoonotic potential. Zoonoses and public health, 56(6?7), 310-325.
2. Gallaher, W. R. (2009). Towards a sane and rational approach to management of Influenza H1N1 2009. Virology journal, 6(1), 1-7.
3. Harrison, S. C. (2008). Viral membrane fusion. Nature structural & molecular biology, 15(7), 690-698.
4. Burmeister, W. P., Ruigrok, R. W., & Cusack, S. (1992). The 2.2 A resolution crystal structure of influenza B neuraminidase and its complex with sialic acid. The EMBO journal, 11(1), 49-56.
5. Crusat, M., & de Jong, M. D. (2007). Neuraminidase inhibitors and their role in avian and pandemic influenza. Antiviral therapy, 12(4 Pt B), 593-602.
6. De Clercq, E. (2006). Antiviral agents active against influenza A viruses. Nature reviews Drug discovery, 5(12), 1015-1025.
7. Alhazmi, M. I. (2015). Molecular docking of selected phytocompounds with H1N1 Proteins. Bioinformation, 11(4), 196.
8. Eiland, L. S., & Eiland, E. H. (2007). Zanamivir for the prevention of influenza in adults and children age 5 years and older. Therapeutics and clinical risk management, 3(3), 461.
9. Heinonen, S., Silvennoinen, H., Lehtinen, P., Vainionpaa, R., Vahlberg, T., Ziegler, T., & Heikkinen, T. (2010). Early oseltamivir treatment of influenza in children 1–3 years of age: a randomized controlled trial. Clinical infectious diseases, 51(8), 887-894.
10. Gupta, C. L., Akhtar, S., Bajpaib, P., Kandpal, K. N., Desai, G. S., & Tiwari, A. K. (2013). Computational modeling and validation studies of 3-D structure of neuraminidase protein of H1N1 influenza A virus and subsequent in silico elucidation of piceid analogues as its potent inhibitors. EXCLI journal, 12, 215.
11. Cooper, N. J., Sutton, A. J., Abrams, K. R., Wailoo, A., Turner, D., & Nicholson, K. G. (2003). Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials. Bmj, 326(7401), 1235.
12. Sahoo, M., Jena, L., Rath, S. N., & Kumar, S. (2016). Identification of suitable natural inhibitor against influenza A (H1N1) neuraminidase protein by molecular docking. Genomics & informatics, 14(3), 96.
13. Jefferson, T., Jones, M. A., Doshi, P., Del Mar, C. B., Hama, R., Thompson, M. J.,& Heneghan, C. J.(2014). Neuraminidase inhibitors for preventing and treating influenza in adults and children. Cochrane database of systematic reviews, (4).
14. Wang, K., Shun?Shin, M., Gill, P., Perera, R., & Harnden, A. (2012). Neuraminidase inhibitors for preventing and treating influenza in children. Cochrane Database of Systematic Reviews, (1).
15. Li, L., Li, Y., Zhang, L., & Hou, T. (2012). Theoretical studies on the susceptibility of oseltamivir against variants of 2009 A/H1N1 influenza neuraminidase. Journal of chemical information and modeling, 52(10), 2715-2729.
16. Han, N., Liu, X., & Mu, Y. (2012). Exploring the mechanism of zanamivir resistance in a neuraminidase mutant: a molecular dynamics study.
17. Narayanan, M. M., Nair, C. B., Sanjeeva, S. K., Rao, P. S., Pullela, P. K., & Barrow, C. J. (2013). Design of multi ligand inhibitors for the swine flu H1N1 neuraminidase binding site. Advances and applications in bioinformatics and chemistry: AABC, 6, 47.
18. Gao, L., Zu, M., Wu, S., Liu, A. L., & Du, G. H. (2011). 3D QSAR and docking study of flavone derivatives as potent inhibitors of influenza H1N1 virus neuraminidase. Bioorganic & medicinal chemistry letters, 21(19), 5964-5970.
19. Cai, Z., Zhang, G., Tang, B., Liu, Y., Fu, X., & Zhang, X. (2015). Promising anti-influenza properties of active constituents of Withania somnifera ayurvedic herb in targeting neuraminidase of H1N1 influenza: computational study. Cell biochemistry and biophysics, 72(3), 727-739.
20. Lee, S. J., Umano, K., Shibamoto, T., & Lee, K. G. (2005). Identification of volatile components in basil (Ocimum basilicum L.) and thyme leaves (Thymus vulgaris L.) and their antioxidant properties. Food Chemistry, 91(1), 131-137.
21. Sundaram, S. S., & Suresh, K. (2019). Medicinal plants used for the treatment of respiratory diseases in Alagar Hills of Madurai district, Tamil Nadu, India. The Pharma Innovation Journal, 8(3), 35-37.
22. Kožíšek, M., Navrátil, V., Rojíková, K., Pokorná, J., Berenguer Albiñana, C., Pachl, P., ... & Konvalinka, J. (2018). DNA-linked inhibitor antibody assay (DIANA) as a new method for screening influenza neuraminidase inhibitors. Biochemical Journal, 475(23), 3847-3860.
23. Maurer-Stroh, S., Ma, J., Lee, R. T. C., Sirota, F. L., & Eisenhaber, F. (2009). Mapping the sequence mutations of the 2009 H1N1 influenza A virus neuraminidase relative to drug and antibody binding sites. Biology direct, 4(1), 1-9.
24. Xu, X., Zhu, X., Dwek, R. A., Stevens, J., & Wilson, I. A. (2008). Structural characterization of the 1918 influenza virus H1N1 neuraminidase. Journal of virology, 82(21), 10493-10501.