A "building block" approach to the new influenza A virus entry inhibitors with reduced cellular toxicities

作者：Lin, Dongguo; Li, Fangfang; Wu, Qiuyi; Xie, Xiangkun; Wu, Wenjiao; Wu, Jie; Chen, Qing; Liu, Shuwen; He, Jian^*

来源：Scientific Reports, 2016, 6(1): 22790.

DOI：10.1038/srep22790

• ANTIMICROBIAL PEPTIDES
• RECEPTOR-BINDING
• HEMAGGLUTININ
• FUSION
• LIPOPEPTIDES
• REPLICATION
• DERIVATIVES
• DISCOVERY
• INFECTION
• PROTEINS

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 mu M 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.

• 出版日期2016-3-8
• 单位南方医科大学; 广东省疾病预防控制中心