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Preparation of monoPEGylated Cyanovirin-N's derivative and its anti-influenza A virus bioactivity in vitro and in vivo
Wu, Chongchao1,2; Chen, Wei1; Chen, Jia1; Han, Bo1,2; Peng, Zhou3; Ge, Feng1,4; Wei, Bo1; Liu, Mingxian1; Zhang, Meiying1; Qian, Chuiwen1; Hou, Zhibo1; Liu, Ge5; Guo, Chaowan5; Wang, Yifei1; Kitazato, Kaio5; Yu, Guoying5; Zou, Chunbin6; Xiong, Sheng1; Xiong, S (reprint author), Jinan Univ, Biomed R&D Ctr, 5-F,Bldg Biol, Guangzhou 510632, Guangdong, Peoples R China.
2015-06-01
Source PublicationJOURNAL OF BIOCHEMISTRY
ISSN0021-924X
Volume157Issue:6Pages:539-548
AbstractInfluenza A virus (IAV) has been raising public health and safety concerns worldwide. Cyanovirin-N (CVN) is a prominent anti-IAV candidate, but both cytotoxicity and immunogenicity have hindered the development of this protein as a viable therapy. In this article, linker-CVN (LCVN) with a flexible and hydrophilic polypeptide at the N-terminus was efficiently produced from the cytoplasm of Escherichia coli at a > 15-l scale. PEGylation at the N-terminal alpha-amine of LCVN was also reformed as 20 kDa PEGylated linkered Cyanovirin-N (PEG(20k)-LCVN). The 50% effective concentrations of PEG(20k)-LCVN were 0.43 +/- 0.11 A mu M for influenza A/HK/8/68 (H3N2) and 0.04 +/- 0.02 A mu M for A/Swan/Hokkaido/51/96 (H5N3), dramatically lower than that of the positive control, Ribavirin (2.88 +/- 0.66 x 10(3) A mu M and 1.79 +/- 0.62 x 10(3) A mu M, respectively). A total of 12.5 A mu M PEG(20k)-LCVN effectively inactivate the propagation of H3N2 in chicken embryos. About 2.0 mg/kg/day PEG(20k)-LCVN increased double the survival rate (66.67%, P = 0.0378) of H3N2 infected mice, prolonged the median survival period, downregulated the mRNA level of viral nuclear protein and decreased (attenuated) the pathology lesion in mice lung. A novel PEGylated CVN derivative, PEG(20k)-LCVN, exhibited potent and strain-dependent anti-IAV activity in nanomolar concentrations in vitro, as well as in micromolar concentration in vivo.
SubtypeArticle
KeywordCyanovirin-n Influenza a Virus Mice Pegylation Polypeptide Linker
Department[Wu, Chongchao ; Chen, Wei ; Chen, Jia ; Han, Bo ; Ge, Feng ; Wei, Bo ; Liu, Mingxian ; Zhang, Meiying ; Qian, Chuiwen ; Hou, Zhibo ; Wang, Yifei ; Xiong, Sheng] Jinan Univ, Inst Biomedicine Natl Engn Res Ctr Genet Med, Dept Cellular Biol, Guangzhou 510632, Guangdong, Peoples R China ; [Wu, Chongchao ; Han, Bo] Shanghai Jiao Tong Univ, Shanghai Ctr Syst Biomed, Minist Educ, Key Lab Syst Biomed, Shanghai 200240, Peoples R China ; [Peng, Zhou] Zhejiang Ocean Univ, Dept Pharm, Coll Food & Pharm Med, Zhoushan 316002, Peoples R China ; [Ge, Feng] Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China ; [Liu, Ge ; Guo, Chaowan ; Kitazato, Kaio ; Yu, Guoying] Nagasaki Univ, Grad Sch Biomed Sci, Dept Mol Microbiol & Immunol, Div Mol Pharmacol Infect Agents, Nagasaki, Nagasaki Prefec 8528521, Japan ; [Zou, Chunbin] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA
DOI10.1093/jb/mvv013
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000356238100013
WOS KeywordTRANSFERRIN FUSION PROTEIN ; COLONY-STIMULATING FACTOR ; MICROBICIDE DEVELOPMENT ; INACTIVATING PROTEIN ; INFLUENZA VACCINES ; PEGYLATION ; EXPRESSION ; EFFICACY ; HIV
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/23969
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorXiong, S (reprint author), Jinan Univ, Biomed R&D Ctr, 5-F,Bldg Biol, Guangzhou 510632, Guangdong, Peoples R China.
Affiliation1.Jinan Univ, Inst Biomedicine Natl Engn Res Ctr Genet Med, Dept Cellular Biol, Guangzhou 510632, Guangdong, Peoples R China
2.Shanghai Jiao Tong Univ, Shanghai Ctr Syst Biomed, Minist Educ, Key Lab Syst Biomed, Shanghai 200240, Peoples R China
3.Zhejiang Ocean Univ, Dept Pharm, Coll Food & Pharm Med, Zhoushan 316002, Peoples R China
4.Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China
5.Nagasaki Univ, Grad Sch Biomed Sci, Dept Mol Microbiol & Immunol, Div Mol Pharmacol Infect Agents, Nagasaki, Nagasaki Prefec 8528521, Japan
6.Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA
Recommended Citation
GB/T 7714
Wu, Chongchao,Chen, Wei,Chen, Jia,et al. Preparation of monoPEGylated Cyanovirin-N's derivative and its anti-influenza A virus bioactivity in vitro and in vivo[J]. JOURNAL OF BIOCHEMISTRY,2015,157(6):539-548.
APA Wu, Chongchao.,Chen, Wei.,Chen, Jia.,Han, Bo.,Peng, Zhou.,...&Xiong, S .(2015).Preparation of monoPEGylated Cyanovirin-N's derivative and its anti-influenza A virus bioactivity in vitro and in vivo.JOURNAL OF BIOCHEMISTRY,157(6),539-548.
MLA Wu, Chongchao,et al."Preparation of monoPEGylated Cyanovirin-N's derivative and its anti-influenza A virus bioactivity in vitro and in vivo".JOURNAL OF BIOCHEMISTRY 157.6(2015):539-548.
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