title: New influenza A Virus Entry Inhibitors Derived from the Viral Fusion Peptides.
abstract: Influenza A viral (IAV) fusion peptides are known for their important role in viral-cell fusion process and membrane destabilization potential which are compatible with those of antimicrobial peptides. Thus, by replacing the negatively or neutrally charged residues of FPs with positively charged lysines, we synthesized several potent antimicrobial peptides derived from the fusogenic peptides (FPs) of hemagglutinin glycoproteins (HAs) of IAV. The biological screening identified that in addition to the potent antibacterial activities, these positively charged fusion peptides (pFPs) effectively inhibited the replication of influenza A viruses including oseltamivir-resistant strain. By employing pseudovirus-based entry inhibition assays including H5N1 influenza A virus (IAV), and VSV-G, the mechanism study indicated that the antiviral activity may be associated with the interactions between the HA2 subunit and pFP, of which, the nascent pFP exerted a strong effect to interrupt the conformational changes of HA2, thereby blocking the entry of viruses into host cells. In addition to providing new peptide "entry blockers", these data also demonstrate a useful strategy in designing potent antibacterial agents, as well as effective viral entry inhibitors. It would be meaningful in treatment of bacterial co-infection during influenza pandemic periods, as well as in our current war against those emerging pathogenic microorganisms such as IAV and HIV.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, P. R. China.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, P. R. China.
authors.forename: Dongguo
authors.initials: D
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, P. R. China.
authors.forename: Xintian
authors.initials: X
authors.lastname: Shen
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, P. R. China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, P. R. China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Fang
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, P. R. China.
authors.forename: Kaiqun
authors.initials: K
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, P. R. China.
authors.forename: Tianrong
authors.initials: T
authors.lastname: Xun
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, P. R. China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, P. R. China.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: He
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D007251:Influenza, Human / Q000188:drug therapy; D065147:Viral Fusion Protein Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014760:Viral Fusion Proteins / Q000378:metabolism*; D053586:Virus Internalization / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D065147:Viral Fusion Protein Inhibitors; D014760:Viral Fusion Proteins