title: A "building block" approach to the new influenza A virus entry inhibitors with reduced cellular toxicities.
abstract: Influenza A virus (IAV) is a severe worldwide threat to public health and economic development that results in the emergence of drug-resistant or highly virulent strains. Therefore, it is imperative to develop potent anti-IAV drugs with different modes of action to currently available drugs. Herein, we show a new class of antiviral peptides generated by conjugating two known short antiviral peptides: part-1 (named Jp with the sequence of ARLPR) and part-2 (named Hp with the sequence of KKWK). The new peptides were thus created by hybridization of these two domains at C- and N- termini, respectively. The anti-IAV screening results identified that C20-Jp-Hp was the most potent peptide with IC50 value of 0.53 μM against A/Puerto Rico/8/34 (H1N1) strain. Interestingly, these new peptides display lower toxicities toward mammalian cells and higher therapeutic indices than their prototypes. In addition, the mechanism of action of C20-Jp-Hp was extensively investigated.
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: 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: Qiuyi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North; Guangzhou 510515, P. R. 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, P. R. China.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Wu
authors.affiliation: Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Guangzhou 511430, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: School of Public Health and Tropical Medicine, Southern Medical University, 1838 Guangzhou Avenue North; Guangzhou 510515, P. R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
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: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004285:Dogs; D024882:Drug Resistance, Viral; D057809:HEK293 Cells; D006387:Hemagglutination, Viral / Q000187:drug effects; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects*; D009981:Influenza B virus / Q000187:drug effects*; D061985:Madin Darby Canine Kidney Cells; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects*; D053585:Virus Attachment / Q000187:drug effects*; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D009439:Neuraminidase