tetano
Editor, Senior Moderator
FEBS J. 2012 Dec 27. doi: 10.1111/febs.12107. [Epub ahead of print]
A peptide derived from C-terminus of PB1 inhibits influenza virus replication by interfering with viral polymerase assembly.
Li C, Ba Q, Wu A, Zhang H, Deng T, Jiang T.
Source
Key Laboratory of Protein & Peptide Pharmaceutical, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, Graduate University of Chinese Academy of Sciences, Beijing, China.
Abstract
Efficient assembly of the influenza virus RNA-dependent RNA polymerase (RdRp), a heterotrimeric complex formed by three subunits PA, PB1 and PB2, is critical for virus replication and pathogenicity. Therefore, interfering with assembly of the RdRp complex could offer novel and effective anti-flu therapeutics. Here we show that a short peptide derived from the amino-acid position 731 to 757 of PB1 (PB1(731-757) ) can disrupt the interaction between the C-terminal part of PB1 (denoted as PB1c that corresponds to PB1(676-757) ) and the N-terminal part of PB2 (denoted as PB2n that corresponds to PB2(1-40) ). We further show that PB1(731-757) is capable of inhibiting the viral polymerase activity and viral replication. Interestingly, we find that the PB1(731-757) interacts with PB1c rather than PB2n. Furthermore, mutational analyses show that hydrophobic sites of PB1c play an essential role in the PB1c-PB1(731-757) interaction. The characterization of the inhibitory effect of PB1(731-757) on viral polymerase activity and viral replication could offer a potential target for anti-flu drug development. ? 2012 The Authors Journal compilation ? 2012 FEBS.
? 2012 The Authors Journal compilation ? 2012 FEBS.
PMID:
23279951
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23279951
A peptide derived from C-terminus of PB1 inhibits influenza virus replication by interfering with viral polymerase assembly.
Li C, Ba Q, Wu A, Zhang H, Deng T, Jiang T.
Source
Key Laboratory of Protein & Peptide Pharmaceutical, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, Graduate University of Chinese Academy of Sciences, Beijing, China.
Abstract
Efficient assembly of the influenza virus RNA-dependent RNA polymerase (RdRp), a heterotrimeric complex formed by three subunits PA, PB1 and PB2, is critical for virus replication and pathogenicity. Therefore, interfering with assembly of the RdRp complex could offer novel and effective anti-flu therapeutics. Here we show that a short peptide derived from the amino-acid position 731 to 757 of PB1 (PB1(731-757) ) can disrupt the interaction between the C-terminal part of PB1 (denoted as PB1c that corresponds to PB1(676-757) ) and the N-terminal part of PB2 (denoted as PB2n that corresponds to PB2(1-40) ). We further show that PB1(731-757) is capable of inhibiting the viral polymerase activity and viral replication. Interestingly, we find that the PB1(731-757) interacts with PB1c rather than PB2n. Furthermore, mutational analyses show that hydrophobic sites of PB1c play an essential role in the PB1c-PB1(731-757) interaction. The characterization of the inhibitory effect of PB1(731-757) on viral polymerase activity and viral replication could offer a potential target for anti-flu drug development. ? 2012 The Authors Journal compilation ? 2012 FEBS.
? 2012 The Authors Journal compilation ? 2012 FEBS.
PMID:
23279951
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23279951