Antonella Pasquato, Cylia Rochat, Dominique J Burri, Giulia Pasqual, Juan Carlos de la Torre, Stefan Kunz
The cellular protease subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in the proteolytic processing of the viral envelope glycoprotein precursor (GPC) of arenaviruses, a step strictly required for production of infectious progeny. The small molecule SKI-1/S1P inhibitor PF-429242 was shown to have anti-viral activity against Old World arenaviruses. Here we extended these studies and show that PF-429242 also inhibits GPC processing and productive infection of New World arenaviruses, making PF-429242 a broadly active anti-arenaviral drug. In combination therapy, PF-429242 potentiated the anti-viral activity of ribavirin, indicating a synergism between the two drugs. A hallmark of arenaviruses is their ability to establish persistent infection in vitro and in vivo. Notably, PF-429242 was able to efficiently and rapidly clear persistent infection by arenaviruses. Interruption of drug treatment did not result in re-emergence of infection, indicating that PF-429242 treatment leads to virus extinction.
J Virol. 2006 Jun;80(12):5897-907
[PMID:
16731928]
J Virol. 2011 Jul;85(14):7246-55
[PMID:
21561907]
Virology. 2003 Mar 30;308(1):37-47
[PMID:
12706088]
Virus Res. 2005 Feb;107(2):165-71
[PMID:
15649562]
Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12701-5
[PMID:
11606739]
Virology. 2011 Aug 15;417(1):18-26
[PMID:
21612810]
Curr Top Microbiol Immunol. 2002;262:75-109
[PMID:
11987809]
J Biol Chem. 1998 Oct 23;273(43):28261-9
[PMID:
9774448]
J Biol Chem. 1998 Mar 6;273(10):5785-93
[PMID:
9488713]
Curr Top Microbiol Immunol. 2002;263:83-117
[PMID:
11987822]
Curr Top Microbiol Immunol. 1987;134:79-116
[PMID:
3034513]
J Biol Chem. 2006 Aug 18;281(33):23471-81
[PMID:
16790437]
J Virol. 2010 Jan;84(1):573-84
[PMID:
19846507]
J Virol. 2008 Aug;82(15):7677-87
[PMID:
18508885]
Nature. 1982 Nov 25;300(5890):360-2
[PMID:
7144891]
J Biol Chem. 2002 Mar 29;277(13):11265-75
[PMID:
11756446]
J Gen Virol. 1983 Aug;64 (Pt 8):1689-98
[PMID:
6875516]
J Gen Virol. 1989 May;70 ( Pt 5):1125-32
[PMID:
2471803]
Mol Cell. 2000 Dec;6(6):1355-64
[PMID:
11163209]
Emerg Infect Dis. 1995 Jul-Sep;1(3):97-100
[PMID:
8903174]
J Virol. 2011 Jan;85(2):795-803
[PMID:
21068251]
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7895-900
[PMID:
12808132]
PLoS Pathog. 2009 May;5(5):e1000455
[PMID:
19478873]
Nat Med. 2004 Dec;10(12 Suppl):S110-21
[PMID:
15577929]
J Virol. 2008 Jun;82(12):6045-51
[PMID:
18400865]
Cell. 1997 May 2;89(3):331-40
[PMID:
9150132]
Am J Obstet Gynecol. 2002 Dec;187(6):1715-6
[PMID:
12501090]
Mol Biol Cell. 2007 Nov;18(11):4493-507
[PMID:
17761532]
J Pharmacol Exp Ther. 2008 Sep;326(3):801-8
[PMID:
18577702]
J Biol Chem. 2004 Apr 23;279(17):17338-47
[PMID:
14970232]
Virology. 2006 Jun 5;349(2):476-91
[PMID:
16574183]
J Virol. 2011 Feb;85(4):1662-70
[PMID:
21106748]
Virology. 2006 Sep 15;353(1):111-20
[PMID:
16797051]
Virology. 2003 Sep 15;314(1):168-78
[PMID:
14517070]
PLoS Pathog. 2008 Apr 18;4(4):e1000047
[PMID:
18421377]
J Biol Chem. 2000 Jan 28;275(4):2349-58
[PMID:
10644685]
J Virol. 2007 Jun;81(11):5685-95
[PMID:
17360738]
Virology. 1981 Aug;113(1):73-85
[PMID:
6267791]
Bioorg Med Chem Lett. 2007 Aug 15;17(16):4411-4
[PMID:
17583500]
PLoS Negl Trop Dis. 2009 Jun 02;3(6):e446
[PMID:
19488405]
J Virol. 2003 Mar;77(5):2866-72
[PMID:
12584310]
Virology. 1988 May;164(1):30-8
[PMID:
2452517]
N Engl J Med. 1986 Jan 2;314(1):20-6
[PMID:
3940312]
Intervirology. 1992;33(1):23-31
[PMID:
1371270]
