Identification of a broad-spectrum arenavirus entry inhibitor.

Journal of Virology
Ryan A LarsonSean M Amberg

Abstract

Several arenaviruses, including Lassa virus (LASV), are causative agents of hemorrhagic fever, for which effective therapeutic options are lacking. The LASV envelope glycoprotein (GP) gene was used to generate lentiviral pseudotypes to identify small-molecule inhibitors of viral entry. A benzimidazole derivative with potent antiviral activity was identified from a high-throughput screen utilizing this strategy. Subsequent lead optimization for antiviral activity identified a modified structure, ST-193, with a 50% inhibitory concentration (IC(50)) of 1.6 nM against LASV pseudotypes. ST-193 inhibited pseudotypes generated with other arenavirus envelopes as well, including the remaining four commonly associated with hemorrhagic fever (IC(50)s for Junín, Machupo, Guanarito, and Sabiá were in the 0.2 to 12 nM range) but exhibited no antiviral activity against pseudotypes incorporating either the GP from the LASV-related arenavirus lymphocytic choriomeningitis virus (LCMV) or the unrelated G protein from vesicular stomatitis virus, at concentrations of up to 10 microM. Determinants of ST-193 sensitivity were mapped through a combination of LASV-LCMV domain-swapping experiments, genetic selection of viral variants, and site-directed m...Continue Reading

References

Aug 1, 1991·The Journal of General Virology·L M AllisonC R Howard
Jan 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·S P Fisher-HochS Bauer
Mar 1, 1987·The Journal of Infectious Diseases·J B McCormickE S Smith
Mar 1, 1987·The Journal of Infectious Diseases·J B McCormickT C Tong
Jan 2, 1986·The New England Journal of Medicine·J B McCormickR Belmont-Williams
Sep 30, 1995·BMJ : British Medical Journal·S P Fisher-HochJ B McCormick
Aug 3, 1995·The New England Journal of Medicine·M BarryC J Peters
Jan 1, 1994·Antiviral Research·D A Enria, J I Maiztegui
Apr 1, 1997·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·P E KilgoreC J Peters
Feb 18, 1998·The Journal of Infectious Diseases·J I MaizteguiC J Peters
Jul 11, 2000·Journal of Virology·S P Fisher-HochJ B McCormick
Aug 25, 2000·MMWR. Morbidity and Mortality Weekly Report·UNKNOWN Centers for Disease Control and Prevention (CDC)
Apr 23, 2002·Journal of Virology·Christina F SpiropoulouMichael B A Oldstone
May 4, 2002·JAMA : the Journal of the American Medical Association·Luciana BorioUNKNOWN Working Group on Civilian Biodefense
Dec 31, 2002·Virology·Angela M Archer, Rebeca Rico-Hesse
Aug 15, 2003·The Journal of Biological Chemistry·Marc FroeschkeBernhard Dobberstein
Mar 20, 2004·Nature Reviews. Drug Discovery·Tom MatthewsDani Bolognesi
May 27, 2005·Antimicrobial Agents and Chemotherapy·Janet L DouglasTomas Cihlar
Jun 24, 2005·PLoS Medicine·Thomas W GeisbertHeinz Feldmann
Dec 16, 2006·Current Medicinal Chemistry·Stefan RussmannGiuseppe Palasciano
Nov 13, 2007·Virology·Therese ReignierPaula M Cannon

❮ Previous
Next ❯

Citations

Nov 12, 2010·The Journal of Biological Chemistry·Klára BriknarováJack H Nunberg
Jul 25, 2009·Journal of Virology·Sudhakar S AgnihothramJack H Nunberg
Jan 29, 2011·Journal of Virology·Arnab BasuTerry L Bowlin
Sep 15, 2010·PLoS Pathogens·Carl J BaldickDaniel J Tenney
Nov 30, 2011·Future Microbiology·Brian B Gowen, Mike Bray
Nov 22, 2012·Viruses·Florencia N LineroElsa B Damonte
Dec 4, 2012·Viruses·Shuzo Urata, Jiro Yasuda
May 23, 2012·Expert Opinion on Drug Discovery·Sheli R RadoshitzkySina Bavari
Jan 18, 2011·Expert Opinion on Investigational Drugs·Aarthi NarayananKylene Kehn-Hall
Aug 9, 2011·Antiviral Research·Juan C ZapataMaria S Salvato
Mar 5, 2011·Antiviral Research·Kathleen A CashmanMary C Guttieri
Mar 2, 2011·Antiviral Research·R N CharrelX de Lamballerie
Aug 17, 2010·Antiviral Research·Mike BrayElaine Jagoda
Jul 14, 2010·Virus Research·Nicolás Cifuentes-MuñozNicole D Tischler
Sep 15, 2009·Veterinary Microbiology·R N Charrel, X de Lamballerie
Feb 18, 2016·Expert Opinion on Drug Discovery·Antonella Pasquato, Stefan Kunz
May 4, 2012·Medicinal Research Reviews·Erik De Clercq
Jun 15, 2012·Molecular Ecology·Nancy R IrwinNatália Martínková
Dec 25, 2010·Virology·Andrew M LeeStefan Kunz
Jan 1, 2015·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·R KerberJ ter Meulen
Aug 27, 2016·Virologica Sinica·Wei WangGengfu Xiao
Feb 6, 2016·PloS One·Josephine A BonventreAleksandra E Sikora
Mar 23, 2017·Revista Da Sociedade Brasileira De Medicina Tropical·Joel Henrique Ellwanger, José Artur Bogo Chies
Apr 17, 2015·Journal of Virology·Guido WollmannAnthony N van den Pol
Feb 26, 2016·Journal of Virology·Yi-Ying ChouRaphaël Gaudin
Jan 11, 2019·Journal of Virology·Giulia TorrianiStefan Kunz
Jun 5, 2010·Expert Review of Anti-infective Therapy·Jae-Min Song, Baik-Lin Seong
Dec 4, 2012·Expert Review of Anti-infective Therapy·Yanchen Zhou, Graham Simmons
Dec 18, 2012·Expert Review of Anti-infective Therapy·Antonella PasquatoStefan Kunz
Jun 25, 2017·Annual Review of Virology·Nicolás Sarute, Susan R Ross
Mar 23, 2019·BMJ Global Health·Laura T Mazzola, Cassandra Kelly-Cirino
Mar 16, 2013·Medicinal Research Reviews·Erik De Clercq

❮ Previous
Next ❯

Related Concepts

Related Feeds

Argentine Hemorrhagic Fever

Argentine hemorrhagic fever (AHF) is an endemo-epidemic disease caused by junín virus (JUNV), a member of the arenaviridae family. Discover the latest research on AHF here.

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.

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.