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Peptide-Mediated Interference of PB2-eIF4G1 Interaction Inhibits Influenza A Viruses’ Replication in Vitro and in Vivo

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journal contribution
posted on 07.06.2016, 00:00 by Shuofeng Yuan, Hin Chu, Jiahui Ye, Meng Hu, Kailash Singh, Billy K. C. Chow, Jie Zhou, Bo-Jian Zheng
Influenza viruses are obligate parasites that hijack the host cellular system. Previous results have shown that the influenza virus PB2 subunit confers a dependence of host eukaryotic translation initiation factor 4-γ 1 (eIF4G1) for viral mRNA translation. Here, we demonstrated that peptide-mediated interference of the PB2-eIF4G1 interaction inhibited virus replication in vitro and in vivo. Remarkably, intranasal administration of the peptide provided 100% protection against lethal challenges of influenza A viruses in BALB/c mice, including H1N1, H5N1, and H7N9 influenza virus subtypes. Mapping of the PB2 protein indicated that the eIF4G1 binding sites resided within the PB2 cap-binding domain. Virtual docking analysis suggested that the inhibitory peptide associated with the conserved amino acid residues that were essential to PB2 cap-binding activity. Overall, our results identified the PB2-eIF4G1 interactive site as a druggable target for influenza therapeutics.