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Inhibitors of Signal Peptide Peptidase (SPP) Affect HSV-1 Infectivity in Vitro and in Vivo

Inhibitors of Signal Peptide Peptidase (SPP) Affect HSV-1 Infectivity in Vitro and in Vivo

Sariah J Allen, Kevin R Mott, Homayon Ghiasi

Exp Eye Res. 2014 Jun;123:8-15.

PMID: 24768597

Abstract:

Recently we have shown that the highly conserved herpes simplex virus glycoprotein K (gK) binds to signal peptide peptidase (SPP), also known as minor histocompatibility antigen H13. In this study we have demonstrated for the first time that inhibitors of SPP, such as L685,458, (Z-LL)2 ketone, aspirin, ibuprofen and DAPT, significantly reduced HSV-1 replication in tissue culture. Inhibition of SPP activity via (Z-LL)2 ketone significantly reduced viral transcripts in the nucleus of infected cells. Finally, when administered during primary infection, (Z-LL)2 ketone inhibitor reduced HSV-1 replication in the eyes of ocularly infected mice. Thus, blocking SPP activity may represent a clinically effective and expedient approach to the reduction of viral replication and the resulting pathology.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP313664403	(Z-LL)2 Ketone		313664-40-3	Price

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