Antiviral drug discovery strategy using combinatorial libraries of structurally constrained peptides

Journal of Virology
E RealY Jacob

Abstract

We have developed a new strategy for antiviral peptide discovery by using lyssaviruses (rabies virus and rabies-related viruses) as models. Based on the mimicry of natural bioactive peptides, two genetically encoded combinatorial peptide libraries composed of intrinsically constrained peptides (coactamers) were designed. Proteomic knowledge concerning the functional network of interactions in the lyssavirus transcription-replication complex highlights the phosphoprotein (P) as a prime target for inhibitors of viral replication. We present an integrated, sequential drug discovery process for selection of peptides with antiviral activity directed against the P. Our approach combines (i). an exhaustive two-hybrid selection of peptides binding two phylogenetically divergent lyssavirus P's, (ii). a functional analysis of protein interaction inhibition in a viral reverse genetic assay, coupled with a physical analysis of viral nucleoprotein-P complex by protein chip mass spectrometry, and (iii). an assay for inhibition of lyssavirus infection in mammalian cells. The validity of this strategy was demonstrated by the identification of four peptides exhibiting an efficient antiviral activity. Our work highlights the importance of P as a...Continue Reading

References

Jul 20, 1990·Science·B M OliveraL J Cruz
Oct 1, 1995·Trends in Biotechnology·B M OliveraD Yoshikami
Sep 1, 1995·The Biochemical Journal·S Hara, M Yamakawa
Apr 11, 1995·Nucleic Acids Research·M YangS Fields
Dec 15, 1995·The Journal of Biological Chemistry·S Hara, M Yamakawa
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·M G Kolonin, R L Finley
Jul 30, 1999·Developmental and Comparative Immunology·P BuletD Hoffmann
Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·M VisintinA Cattaneo
Oct 12, 2000·Journal of Virology·H RauxD Blondel
Oct 12, 2000·Journal of Virology·Y JacobN Tordo
Jan 18, 2002·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Henry WildeVisith Sitprija
Jun 21, 2002·Methods in Enzymology·Micheline Fromont-RacinePierre Legrain

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Citations

Jan 16, 2014·Indian Journal of Virology : an Official Organ of Indian Virological Society·Vinay Ganeshrao JoshiSatish Kumar
May 29, 2012·Nucleic Acids Research·Nishant ThakurManoj Kumar
Jul 29, 2009·PLoS Neglected Tropical Diseases·Charles E Rupprecht
Jan 30, 2013·PloS One·Abid QureshiManoj Kumar
Oct 23, 2013·PloS One·Rogelio López-MartínezBlanca L Barrón
Mar 14, 2009·The International Journal of Neuroscience·Nadia Y CastanedaJaime E Castellanos
Aug 26, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Angélique LewiesDu Plessis Lissinda Hester
May 31, 2006·Expert Opinion on Investigational Drugs·Kathryn TaylorCaroline Dive
Jul 10, 2012·International Immunopharmacology·Hong-Ru LiangXian-Zhu Xia
Nov 6, 2009·PLoS Neglected Tropical Diseases·Thomas MüllerMarie Paule Kieny
Feb 5, 2008·Antiviral Research·Alla TrahtenhertsItai Benhar
Jul 1, 2008·Advances in Virus Research·Susan A Nadin-Davis, Christine Fehlner-Gardiner
Jan 13, 2009·Journal of Biotechnology·Rim BenmaamarCarlos Augusto Pereira
Nov 19, 2011·Antiviral Chemistry & Chemotherapy·Hongbing JiangTetsuya Toyoda
Dec 19, 2014·Angewandte Chemie·Korbinian BrunnerThomas Carell
Nov 23, 2007·Critical Reviews in Microbiology·Louis H Nel, Wanda Markotter
May 21, 2020·International Journal of Peptide Research and Therapeutics·Yongzhong LuJie Liu

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