Insilico Identification of H5N1 Avian Influenza Neuraminidase Inhibitors

Abstract

Background: H5N1 avian influenza virus is influenza-A virus subtype that is highly contagious and fatal among birds and humans. Although human-human transmission of H5N1 is rare, but once the virus has acquired this ability, a devastating pandemic may be inevitable. The virus is currently in WHO phase 3 pandemic alerts: A new influenza virus subtype causing disease in humans, but is yet to spread efficiently and sustainably among humans. Oseltamivir is a single most-win WHO recommended drug for the treatment and prophylaxis of H5N1 influenza virus infection. However, several oseltamivir resistant strains of H5N1 have been reported. Methods: In silico molecular docking algorithm and pharmacophore modelling simulations were used to identify a novel H5N1 avian influenza neuraminidase inhibitors. Results: Of the 518-neuraminidase analogue, five (eflornithine, eltrombopag, entecavir, aminosalicylic acid and pregabalin) demonstrated excellent binding affinities against viral neuraminidase similar to that of oseltamivir. Again, these drugs like oseltamivir interact mainly with arginine, tyrosine and glutamine at different positions of the neuraminidase. Similarly, oseltamivir and the five selected drugs superimpose to the active pocket of neuraminidase, further buttressing the previous findings. Furthermore, oseltamivir and the five drugs had common generated pharmacophores. Conclusion: This study was the first to demonstrate the anti-viral neuraminidase effect of eflornithine, eltrombopag, entecavir, aminosalicylic acid and pregabalin. Keywords: Neuraminidase, Oseltamivir, H5N1 avian influenza, Pharmacophore, molecular docking.