Specific inhibition of bovine viral diarrhea virus replicase

Journal of Virology
Jin-Hua SunMin Gao

Abstract

Compound-1453 was identified and characterized as a specific inhibitor of bovine viral diarrhea virus (BVDV). The concentration of compound-1453 which results in 50% protection from virus-induced cytopathic effect is approximately 2.2 microM, with a therapeutic index of 60, and it is not active against a panel of RNA and DNA viruses. A time-of-addition experiment suggested that compound-1453 targets a stage of the viral life cycle after viral entry. To determine the target of compound-1453, resistant virus was generated. Resistant variants grew efficiently in the presence or absence of 33 micro M compound-1453 and exhibited replication efficiency in the presence of compound-1453 approximately 1,000-fold higher than that of the wild-type (wt) virus. Functional mapping and sequence analysis of resistant cDNAs revealed a single amino acid substitution (Glu to Gly) at residue 291 in the NS5B polymerase in all eight independently generated cDNA clones. Recombinant virus containing this single mutation retained the resistance phenotype and a replication efficiency similar to that of the original isolated resistant virus. Since compound-1453 did not inhibit BVDV polymerase activity in vitro (50% inhibitory concentration > 300 microM),...Continue Reading

References

Mar 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·R A KrzyzekA J Faras
Jan 1, 1979·Annual Review of Biochemistry·T Blumenthal, G G Carmichael
Mar 1, 1992·Molecular and Cellular Biology·M Gao, D M Knipe
Jan 1, 1987·Advances in Virus Research·E G Westaway
Apr 1, 1974·Proceedings of the Society for Experimental Biology and Medicine·A S Lubiniecki, C J Henry
Jan 1, 1980·Archives of Virology·P A Nuttall
Mar 1, 1995·Journal of Virology·P Warrener, M S Collett
Sep 1, 1994·Microbiological Reviews·J H Strauss, E G Strauss
Jan 1, 1993·Annual Review of Genetics·E WimmerX Cao
Jan 1, 1993·Archives of Virology·A I Bartholomeusz, P J Wright
Jan 4, 1993·Journal of Immunological Methods·D SladowskiM Balls
Nov 1, 1995·The Veterinary Clinics of North America. Food Animal Practice·R O Donis
Sep 1, 1995·Analytical Biochemistry·J H Sun, C C Kao
Jan 1, 1996·Advances in Virus Research·G Meyers, H J Thiel
Jul 1, 1997·Journal of Virology·N TautzH J Thiel
Mar 14, 1998·Journal of Virology·S E BehrensN Tautz
Jun 28, 2000·Proceedings of the National Academy of Sciences of the United States of America·S G BaginskiM S Collett

❮ Previous
Next ❯

Citations

Apr 12, 2013·Journal of Medicinal Chemistry·Denis R St LaurentLawrence B Snyder
Sep 17, 2004·Nature Reviews. Microbiology·Erik De Clercq
Sep 15, 2010·PLoS Pathogens·Carl J BaldickDaniel J Tenney
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Kyung H ChoiMichael G Rossmann
May 31, 2011·Antiviral Research·Michele TonelliPaolo La Colla
Sep 15, 2009·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Ni ZhangYi Lv
Sep 2, 2009·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Ni ZhangGuoyu Zhang
Oct 21, 2015·Canadian Journal of Microbiology·Yan Li, Zexiao Yang
Aug 30, 2005·Current Opinion in Microbiology·Erik De Clercq
Jul 31, 2013·Virology·Donald R O'Boyle IiMin Gao

❮ Previous
Next ❯

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.