Inhibition of Influenza Virus Replication by Constrained Peptides Targeting Nucleoprotein
| Autor: | Yves Jacob, Hongxing Hu, Shijian Zhang, Yidong Xu, Li Li, Hongbing Jiang, Qiang Wang, Tetsuya Toyoda, Leiyun Weng, Ying He, Baosen Jia |
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| Přispěvatelé: | Key Laboratory of Molecular Virology & Immunology (LMVI), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Shanghai Medical College, Fudan University [Shanghai], Roche R&D Center China Ltd, Génétique, Papillomavirus et Cancer Humain, Institut Pasteur [Paris], Choju Medical Institute, Fukushimura Hospital, Infectious Disease Regulation Project, Tokyo Metropolitan Institute of Medical Sciences, This work was supported by Grants-in-aid from the Chinese Academy of Sciences (0514P51131), the National Science Foundation of China (30670090 and 30970153), the Li Ka Shing Foundation (0682P11131), RESPARI (0581P14131) and FLUINNATE (SP5B-CT-2006-0044161)., Institut Pasteur [Paris] (IP), Tokyo Metropolitan Institute of Medical Science (TMIMS) |
| Rok vydání: | 2011 |
| Předmět: |
Mutation rate
viruses RNA-binding protein Virus Replication MESH: Dogs Mice Influenza A Virus H1N1 Subtype [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Chlorocebus aethiops MESH: Animals Mice Inbred BALB C 0303 health sciences MESH: Peptides Viral Core Proteins MESH: Influenza Human RNA-Binding Proteins virus diseases General Medicine Nucleocapsid Proteins 3. Good health MESH: HEK293 Cells [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology Female MESH: Antiviral Agents MESH: Viral Core Proteins MESH: Mice Inbred BALB C MESH: Vero Cells Biology Antiviral Agents Virus MESH: Influenza A Virus H1N1 Subtype 03 medical and health sciences Dogs Peptide Library Influenza Human Animals Humans Peptide library Vero Cells MESH: Mice 030304 developmental biology MESH: Humans 030306 microbiology MESH: Virus Replication HEK 293 cells MESH: Cercopithecus aethiops Virology Nucleoprotein HEK293 Cells MESH: RNA-Binding Proteins Viral replication Vero cell MESH: Peptide Library Peptides MESH: Female |
| Zdroj: | Antiviral Chemistry and Chemotherapy Antiviral Chemistry and Chemotherapy, International Medical Press, 2011, 22 (3), pp.119-30. ⟨10.3851/IMP1902⟩ Antiviral Chemistry and Chemotherapy, 2011, 22 (3), pp.119-30. ⟨10.3851/IMP1902⟩ |
| ISSN: | 2040-2066 0956-3202 |
| DOI: | 10.3851/imp1902 |
| Popis: | Background: Because of high mutation rates, new drug-resistant viruses are rapidly evolving, thus making the necessary control of influenza virus infection difficult. Methods: We screened a constrained cysteine-rich peptide library mimicking μ-conotoxins from Conus geographus and a proline-rich peptide library mimicking lebocin 1 and 2 from Bombyx mori by using influenza virus RNA polymerase (PB1, PB2 and PA) and nucleoprotein (NP) as baits. Results: Among the 22 peptides selected from the libraries, we found that the NP-binding proline-rich peptide, PPWCCCSPMKRASPPPAQSDLPATPKCPP, inhibited influenza replicon activity to mean ±SD 40.7% ±15.8% when expressed as a GFP fusion peptide in replicon cells. Moreover, when the GFP fusion peptide was transduced into cells by an HIV-TAT protein transduction domain sequence, the replication of influenza virus A/WSN/33 (WSN) at a multiplicity of infection of 0.01 was inhibited to 20% and 69% at 12 and 24 h post-infection, respectively. In addition, the TAT-GFP fusion peptide was able to slightly protect Balb/c mice from WSN infection when administrated prior to the infection. Conclusions: These results suggest the potential of this peptide as the seed of an anti-influenza drug and reveal the usefulness of the constrained peptide strategy for generating inhibitors of influenza infection. The results also suggest that influenza NP, which is conserved among the influenza A viruses, is a good target for influenza inhibition, despite being the most abundant protein in infected cells. |
| Databáze: | OpenAIRE |
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