Antiviral activity and mechanism of ESC-1GN from skin secretion of Hylarana guentheri against influenza A virus

被引:7
作者
Yang, Jie [1 ,2 ]
Zhang, Bei [1 ,2 ]
Huang, Yingna [1 ,2 ]
Liu, Teng [1 ,2 ]
Zeng, Baishuang [1 ,2 ]
Chai, Jinwei [1 ,2 ]
Wu, Jiena [1 ,2 ]
Xu, Xueqing [1 ,2 ]
机构
[1] Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Shatai Nan Rd 1023-1063, Guangzhou 510515, Guangdong, Peoples R China
[2] Southern Med Univ, Guangzhou Key Lab Drug Res Emerging Virus Prevent, Sch Pharmaceut Sci, Shatai Nan Rd 1023-1063, Guangzhou 510515, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
amphibian; antimicrobial peptide; ESC-1GN; haemagglutinin; influenza A virus; H5N1 AVIAN INFLUENZA; ANTIMICROBIAL PEPTIDES; INFECTION; HEMAGGLUTININ; FROG; RESISTANCE; STABILITY;
D O I
10.1093/jb/mvab019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Development of new and effective antiinfluenza drugs is critical for prophylaxis and treatment of influenza A virus (IAV) infection. A wide range of amphibian skin secretions have been identified to show antiviral activity. Our previously reported ESC-1GN, a peptide from the skin secretion of Hylarana guentheri, displayed good antimicrobial and antiinflammatory effects. Here, we found that ESC-1GN possessed significant antiviral effects against IAVs. Moreover, ESC-1GN could inhibit the entry of divergent H5N1 and H1N1 virus strains with the IC50 values from 1.29 to 4.59(mu)M. Mechanism studies demonstrated that ESC-1GN disrupted membrane fusion activity of IAVs by interaction with HA2 subunit. The results of site-directed mutant assay and molecular docking revealed that E105, N50 and the residues around them on HA2 subunit could form hydrogen bonds with amino acid on ESC-1GN, which were critical for ESC-1GN binding to HA2 and inhibiting the entry of IAVs. Altogether, these not only suggest that ESC-1GN maybe represent a new type of excellent template designing drugs against IAVs, but also it may shed light on the immune mechanism and survival strategy of H.guentheri against viral pathogens. [GRAPHICS] .
引用
收藏
页码:757 / 765
页数:9
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