tetano
Editor, Senior Moderator
J Biochem. 2015 Feb 20. pii: mvv013. [Epub ahead of print]
[h=1]Preparation of monoPEGylated Cyanovirin-N's derivative and its anti-influenza A virus bioactivity in vitro and in vivo.[/h] Wu C[SUP]1[/SUP], Chen W[SUP]2[/SUP], Chen J[SUP]2[/SUP], Han B[SUP]1[/SUP], Peng Z[SUP]3[/SUP], Ge F[SUP]4[/SUP], Wei B[SUP]2[/SUP], Liu M[SUP]2[/SUP], Zhang M[SUP]2[/SUP], Qian C[SUP]2[/SUP], Hou Z[SUP]2[/SUP], Liu G[SUP]5[/SUP], Guo C[SUP]5[/SUP], Wang Y[SUP]2[/SUP], Kitazato K[SUP]5[/SUP], Yu G[SUP]5[/SUP], Zou C[SUP]6[/SUP], Xiong S[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza 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 paper, linker-CVN (LCVN) with a flexible and hydrophilic polypeptide at the N-terminus was efficiently produced from the cytoplasm of Escherichia coli (E. coli) at a >15 liter scale. PEGylation at the N-terminal α-amine of LCVN was also reformed as PEG[SUB]20k[/SUB]-LCVN. The 50 % effective concentrations of PEG[SUB]20k[/SUB]-LCVN were 0.43?0.11 μM for influenza A/HK/8/68 (H3N2) and 0.04?0.02 μM for A/Swan/Hokkaido/51/96 (H5N3), dramatically lower than that of the positive control, Ribavirin (2.88?0.66 ? 10[SUP]3[/SUP] μM and 1.79?0.62 ? 10[SUP]3[/SUP] μM, respectively). 12.5 μM PEG[SUB]20k[/SUB]-LCVN effectively inactivate the propagation of H3N2 in chicken embryos. 2.0 mg/kg/day PEG[SUB]20k[/SUB]-LCVN increased double the survival rate (66.67 %, p=0.0378) of H3N2 infected mice, prolonged the median survival period, down-regulated the mRNA level of viral nuclear protein and decreased (attenuated) the pathology lesion in mice lung. A novel PEGylated CVN derivative, PEG[SUB]20k[/SUB]-LCVN, exhibited potent and strain-dependent anti-IAV activity in nM concentrations in vitro, as well as in μM concentration in vivo.
? The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.
[h=4]KEYWORDS:[/h] Cyanovirin-N; PEGylation; influenza A virus; mice; polypeptide linker
PMID: 25713409 [PubMed - as supplied by publisher]
[h=1]Preparation of monoPEGylated Cyanovirin-N's derivative and its anti-influenza A virus bioactivity in vitro and in vivo.[/h] Wu C[SUP]1[/SUP], Chen W[SUP]2[/SUP], Chen J[SUP]2[/SUP], Han B[SUP]1[/SUP], Peng Z[SUP]3[/SUP], Ge F[SUP]4[/SUP], Wei B[SUP]2[/SUP], Liu M[SUP]2[/SUP], Zhang M[SUP]2[/SUP], Qian C[SUP]2[/SUP], Hou Z[SUP]2[/SUP], Liu G[SUP]5[/SUP], Guo C[SUP]5[/SUP], Wang Y[SUP]2[/SUP], Kitazato K[SUP]5[/SUP], Yu G[SUP]5[/SUP], Zou C[SUP]6[/SUP], Xiong S[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza 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 paper, linker-CVN (LCVN) with a flexible and hydrophilic polypeptide at the N-terminus was efficiently produced from the cytoplasm of Escherichia coli (E. coli) at a >15 liter scale. PEGylation at the N-terminal α-amine of LCVN was also reformed as PEG[SUB]20k[/SUB]-LCVN. The 50 % effective concentrations of PEG[SUB]20k[/SUB]-LCVN were 0.43?0.11 μM for influenza A/HK/8/68 (H3N2) and 0.04?0.02 μM for A/Swan/Hokkaido/51/96 (H5N3), dramatically lower than that of the positive control, Ribavirin (2.88?0.66 ? 10[SUP]3[/SUP] μM and 1.79?0.62 ? 10[SUP]3[/SUP] μM, respectively). 12.5 μM PEG[SUB]20k[/SUB]-LCVN effectively inactivate the propagation of H3N2 in chicken embryos. 2.0 mg/kg/day PEG[SUB]20k[/SUB]-LCVN increased double the survival rate (66.67 %, p=0.0378) of H3N2 infected mice, prolonged the median survival period, down-regulated the mRNA level of viral nuclear protein and decreased (attenuated) the pathology lesion in mice lung. A novel PEGylated CVN derivative, PEG[SUB]20k[/SUB]-LCVN, exhibited potent and strain-dependent anti-IAV activity in nM concentrations in vitro, as well as in μM concentration in vivo.
? The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.
[h=4]KEYWORDS:[/h] Cyanovirin-N; PEGylation; influenza A virus; mice; polypeptide linker
PMID: 25713409 [PubMed - as supplied by publisher]