Discovery of Influenza A Virus Sequence Pairs and Their Combinations for Simultaneous Heterosubtypic Targeting that Hedge against Antiviral Resistance

PLoS Computational Biology
Keng Boon WeeSebastian Maurer-Stroh

Abstract

The multiple circulating human influenza A virus subtypes coupled with the perpetual genomic mutations and segment reassortment events challenge the development of effective therapeutics. The capacity to drug most RNAs motivates the investigation on viral RNA targets. 123,060 segment sequences from 35,938 strains of the most prevalent subtypes also infecting humans-H1N1, 2009 pandemic H1N1, H3N2, H5N1 and H7N9, were used to identify 1,183 conserved RNA target sequences (≥15-mer) in the internal segments. 100% theoretical coverage in simultaneous heterosubtypic targeting is achieved by pairing specific sequences from the same segment ("Duals") or from two segments ("Doubles"); 1,662 Duals and 28,463 Doubles identified. By combining specific Duals and/or Doubles to form a target graph wherein an edge connecting two vertices (target sequences) represents a Dual or Double, it is possible to hedge against antiviral resistance besides maintaining 100% heterosubtypic coverage. To evaluate the hedging potential, we define the hedge-factor as the minimum number of resistant target sequences that will render the graph to become resistant i.e. eliminate all the edges therein; a target sequence or a graph is considered resistant when it ca...Continue Reading

References

May 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J M LeiterP C Zamecnik
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·D Plehn-Dujowich, S Altman
Sep 5, 2002·Nature Reviews. Drug Discovery·Andrew L Hopkins, Colin R Groom
Apr 2, 2003·Nature Reviews. Drug Discovery·Janet Dancey, Edward A Sausville
Apr 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Andrew I SuJohn B Hogenesch
Jun 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Stephen Mark TompkinsSuzanne L Epstein
Jun 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Qing GeJianzhu Chen
Feb 4, 2006·JAMA : the Journal of the American Medical Association·Rick A BrightAlexander I Klimov
Feb 9, 2006·PLoS Biology·Henry Nicholls
Sep 13, 2006·Antimicrobial Agents and Chemotherapy·Qing GeDavid A Stein
Dec 2, 2006·Nature Reviews. Drug Discovery·Erik De Clercq
Dec 14, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·P L HardingS D Wilton
Apr 5, 2007·JAMA : the Journal of the American Medical Association·Shuji HatakeyamaYoshihiro Kawaoka
Nov 13, 2007·Biochemical and Biophysical Research Communications·Yanhua WuMing Wang
Mar 29, 2008·Archives of Virology·Christopher LupferManoj Pastey
Nov 27, 2008·Archives of Virology·Terry KwokKarin Moelling
Jan 13, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Iain StephensonMaria Zambon
Jan 15, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Linda J PopplewellIan R Graham
Apr 17, 2009·The Journal of General Virology·Walter de VriesBen Berkhout
Jan 1, 2010·Nature Reviews. Drug Discovery·Aimee L Jackson, Peter S Linsley
Sep 23, 2010·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Ha T NguyenLarisa V Gubareva
Sep 30, 2010·Emerging Infectious Diseases·Masafumi InoueCui Lin
Oct 1, 2010·The New England Journal of Medicine·Erhard van der VriesCharles A B Boucher
Dec 24, 2010·Nucleic Acids Research·Niranjan Nagarajan, Carl Kingsford
Jan 21, 2012·Nature Reviews. Drug Discovery·Ryszard KoleSidney Altman
Apr 26, 2012·Bioinformatics·Joshua TanSebastian Maurer-Stroh
Jun 23, 2012·Science·Sander HerfstRon A M Fouchier

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Citations

Dec 18, 2016·Archives of Medical Research·Jose Luis Sandoval-Gutierrez

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Methods Mentioned

BETA
antisense oligonucleotides

Software Mentioned

blastn
Java
Perl scripts

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