Design, synthesis and antiviral evaluation of phenyl piperazine c | 3362
Virology & Mycology

Virology & Mycology
Open Access

ISSN: 2161-0517

Design, synthesis and antiviral evaluation of phenyl piperazine containing benzyl trizole derivatives against pandemic swine flu (H1N1) influenza virus

International Conference on Flu

June 08-10, 2015 Chicago, USA

Gaurav Joshi and Manmohan Parida

Posters-Accepted Abstracts: Virol-mycol

Abstract :

The pandemic swine flu virus (H1N1pdm) continues to be a global health concern with the emergence of antigenically shifted highly virulent strains. The development of Oseltamivir and Nucleozin resistant strains has demanded for conserved antiviral target and novel drugs for control of H1N1pdm infection. The aim of this study was to screen phenyl piperazine containing benzyl trizole derivatives against H1N1pdm infection.Based on docking studies and structure activity relationship, a series of 14 nucleocapsid proteins (NP) antagonist (DC-3 to DC-16) were designed, synthesized using phenyl piperazine containing benzyl trizole as a lead molecule. These inhibitors were evaluated for their in vitro (in MDCK Cells) and in vivo (in BALB/c mice) antiviral efficacy against H1N1pdm virus through various assay. Among all the molecules, DC-12 was the most potent inhibitor with IC50 value 4.6±0.23 μM with a selectivity index 15.5 better than Nucleozin, the known NP antagonist. The protective efficacy of DC-12 was further established through reduction in viral nucleocapsid mRNA and protein expression. Moreover, the treatment of BALB/c mice with DC-12 following infection resulted in reduced pathogenesis as indicated through increased survivability and more than 99.9% reduction in lung viral titre. Furthermore, the docking analysis and in vitro drug resistance test also confirmed that DC-12 not only assumes more favourable conformation at the binding pocket of NP but also overcome the problem of Nucleozin resistance. These findings clearly suggested that DC-12 is a promising small molecule inhibitor for control of H1N1pdm virus including the newly emerged drug resistance strains.