tetano
Editor, Senior Moderator
ACS Infect Dis. 2016 Jul 8;2(7):471-7. doi: 10.1021/acsinfecdis.6b00064. Epub 2016 Jun 13.
[h=1]Peptide-Mediated Interference of PB2-eIF4G1 Interaction Inhibits Influenza A Viruses' Replication in Vitro and in Vivo.[/h] Yuan S[SUP]1[/SUP], Chu H[SUP]1[/SUP], Ye J[SUP]1[/SUP], Hu M[SUP]1[/SUP], Singh K[SUP]2[/SUP], Chow BK[SUP]2[/SUP], Zhou J[SUP]1[/SUP], Zheng BJ[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] PB2; Tat; antiviral peptide; eIF4G1; host−virus interaction; influenza virus
PMID: 27626099 DOI: 10.1021/acsinfecdis.6b00064
[PubMed - in process]
[h=1]Peptide-Mediated Interference of PB2-eIF4G1 Interaction Inhibits Influenza A Viruses' Replication in Vitro and in Vivo.[/h] Yuan S[SUP]1[/SUP], Chu H[SUP]1[/SUP], Ye J[SUP]1[/SUP], Hu M[SUP]1[/SUP], Singh K[SUP]2[/SUP], Chow BK[SUP]2[/SUP], Zhou J[SUP]1[/SUP], Zheng BJ[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] PB2; Tat; antiviral peptide; eIF4G1; host−virus interaction; influenza virus
PMID: 27626099 DOI: 10.1021/acsinfecdis.6b00064
[PubMed - in process]