Inhibition of encephalomyocarditis virus and poliovirus replication by quinacrine: implications for the design and discovery of novel antiviral drugs.

Journal of Virology
Alexander V GasparianAnton A Komar

Abstract

The 9-aminoacridine (9AA) derivative quinacrine (QC) has a long history of safe human use as an antiprotozoal and antirheumatic agent. QC intercalates into DNA and RNA and can inhibit DNA replication, RNA transcription, and protein synthesis. The extent of QC intercalation into RNA depends on the complexity of its secondary and tertiary structure. Internal ribosome entry sites (IRESs) that are required for initiation of translation of some viral and cellular mRNAs typically have complex structures. Recent work has shown that some intercalating drugs, including QC, are capable of inhibiting hepatitis C virus IRES-mediated translation in a cell-free system. Here, we show that QC suppresses translation directed by the encephalomyocarditis virus (EMCV) and poliovirus IRESs in a cell-free system and in virus-infected HeLa cells. In contrast, IRESs present in the mammalian p53 transcript that are predicted to have less-complex structures were not sensitive to QC. Inhibition of IRES-mediated translation by QC correlated with the affinity of binding between QC and the particular IRES. Expression of viral capsid proteins, replication of viral RNAs, and production of virus were all strongly inhibited by QC (and 9AA). These results sugges...Continue Reading

References

Sep 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·H TowbinJ Gordon
Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·J C AlwineG R Stark
Dec 15, 1979·Biochemical Pharmacology·D Bogdanovsky, M Pierre
Dec 1, 1989·European Journal of Cancer & Clinical Oncology·G J FinlayB C Baguley
May 1, 1989·Seminars in Arthritis and Rheumatism·D J Wallace
Jun 1, 1966·Proceedings of the National Academy of Sciences of the United States of America·R L O'BrienF E Hahn
May 5, 1967·Science·J Ciak, F E Hahn
Sep 4, 1996·Biochemical and Biophysical Research Communications·M C JiangS S Chen
Jan 9, 2001·Clinical Microbiology Reviews·T B Gardner, D R Hill
Jul 11, 2001·Genes & Development·C U Hellen, P Sarnow
Aug 10, 2001·Methods in Enzymology·J Ren, J B Chaires
Aug 28, 2003·Current Opinion in Microbiology·Isabel S Novella
Feb 11, 2004·Nucleic Acids Research·Olivia NovacJerry Pelletier
Aug 24, 2004·Current Pharmaceutical Design·Frank RomanelliArdis Dee Hoven
Oct 27, 2004·Bioorganic & Medicinal Chemistry Letters·Zhaohui Yan, Anne M Baranger
Dec 29, 2004·FEBS Letters·Abba MalinaJerry Pelletier
Mar 8, 2005·The Journal of Biological Chemistry·Anton A Komar, Maria Hatzoglou
Apr 28, 2005·Current Pharmaceutical Design·U Barry, Z Zuo
Aug 17, 2005·Current Medicinal Chemistry. Anti-cancer Agents·Jonathan B Chaires
Nov 16, 2005·Nature Medicine·Anna A SablinaPeter M Chumakov
Nov 17, 2005·Proceedings of the National Academy of Sciences of the United States of America·Katerina V GurovaAndrei V Gudkov
Jan 28, 2006·EMBO Reports·Partho Sarothi RaySaumitra Das
Sep 8, 2006·RNA·Stephen D BairdMartin Holcik
Mar 22, 2007·The Journal of General Virology·Puay-Wah PhuanBarnaby C H May
Jan 29, 2008·Inflammation & Allergy Drug Targets·Siquan SunLars Karlsson
Oct 18, 2008·Current Opinion in Chemical Biology·Inna ShcherbakovaMichael Brenowitz
Apr 14, 2009·Current Opinion in Structural Biology·Megan E Filbin, Jeffrey S Kieft
Jul 28, 2009·Biochimica Et Biophysica Acta·Laurent BalvayThéophile Ohlmann
Sep 29, 2009·Biochimica Et Biophysica Acta·Ying LiuAniko V Paul

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Citations

May 31, 2011·Antiviral Research·Michele TonelliPaolo La Colla
Mar 11, 2018·Biochemistry. Biokhimii︠a︡·O S NikonovE Yu Nikonova
Nov 6, 2015·Frontiers in Oncology·Anton A Komar, Maria Hatzoglou
Jul 15, 2016·Science Translational Medicine·Yu MiyazakiChristopher M Gomez
Feb 26, 2021·Scientific Reports·Sinead M O'DonovanRobert E McCullumsmith
Jun 23, 2021·Archives of Medical Research·Benjamin Pineda
Jul 4, 2020·Microbial Pathogenesis·Emanuelle Machado MarinhoHélio Vitoriano Nobre Júnior

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