title: Super short membrane-active lipopeptides inhibiting the entry of influenza A virus.
abstract: Influenza A viruses (IAV) are significant pathogens that result in millions of human infections and impose a substantial health and economic burdens worldwide. Due to the limited anti-influenza A therapeutics available and the emergence of drug resistant viral strains, it is imperative to develop potent anti-IAV agents with different mode of action. In this study, by applying a pseudovirus based screening approach, two super short membrane-active lipopeptides of C12-KKWK and C12-OOWO were identified as effective anti-IAV agents with IC50 value of 7.30±1.57 and 8.48±0.74 mg/L against A/Puerto Rico/8/34 strain, and 6.14±1.45 and 7.22±0.67 mg/L against A/Aichi/2/68 strain, respectively. The mechanism study indicated that the anti-IAV activity of these peptides would result from the inhibition of virus entry by interacting with HA2 subunit of hemagglutinin (HA). Thus, these peptides may have potentials as lead peptides for the development of new anti-IAV therapeutics to block the entry of virus into host cells.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR 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, PR China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR 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, PR China.
authors.forename: Linqing
authors.initials: L
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR China.
authors.forename: Xiangkun
authors.initials: X
authors.lastname: Xie
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR 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, PR China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR China.
authors.forename: Qiuyi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR 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, PR China. Electronic address: jianhe@smu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR China. Electronic address: liusw@smu.edu.cn.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000502:physiology*; D007928:Lethal Dose 50; D055666:Lipopeptides / Q000008:administration & dosage* / Q000138:chemical synthesis*; D061985:Madin Darby Canine Kidney Cells; D008970:Molecular Weight; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D055666:Lipopeptides
keywords: Fusion inhibition; Influenza A virus; Membrane fusion; Short lipopeptide; Virus entry inhibitor; Virus–cell fusion