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Planta Med 2024; 90(15): 1156-1166
DOI: 10.1055/a-2441-6570
Biological and Pharmacological Activity
Original Papers

Aescin Inhibits Herpes simplex Virus Type 1 Induced Membrane Fusion

Diana Ulrich
1   Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Münster, Germany
,
Andreas Hensel 
1   Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Münster, Germany
,
Nica Classen
1   Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Münster, Germany
,
Wali Hafezi
2   Institute of Virology Münster (IVM), University of Münster, Münster, Germany
,
Jandirk Sendker
1   Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Münster, Germany
,
Joachim Kühn
2   Institute of Virology Münster (IVM), University of Münster, Münster, Germany
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Abstract

Infections with Herpes simplex virus can cause severe ocular diseases and encephalitis. The present study aimed to investigate potential inhibitors of fusion between HSV-1 and the cellular membrane of the host cell. Fusion and entry of HSV-1 into the host cell is mimicked by a virus-free eukaryotic cell culture system by co-expression of the HSV-1 glycoproteins gD, gH, gL, and gB in presence of a gD receptor, resulting in excessive membrane fusion and polykaryocyte formation. A microscopic read-out was used for the screening of potential inhibitors, whereas luminometric quantification of cell-cell fusion was used in a reporter fusion assay. HSV-1 gB was tagged at its C-terminus with mCherry to express mCherry-gB in both assay systems for the visualization of the polykaryocyte formation. Reporter protein expression of SEAP was regulated by a Tet-On 3 G system. The saponin mixture aescin was identified as the specific inhibitor (IC50 7.4 µM, CC50 24.3 µM, SI 3.3) of membrane fusion. A plaque reduction assay on Vero cells reduced HSV-1 entry into cells and HSV-1 cell-to-cell spread significantly; 15 µM aescin decreased relative plaque counts to 41%, and 10 µM aescin resulted in a residual plaque size of 11% (HSV-1 17 syn+) and 2% (HSV-1 ANG path). Release of the HSV-1 progeny virus was reduced by one log step in the presence of 15 µM aescin. Virus particle integrity was mainly unaffected. Analytical investigation of aescin by UHPLC-MS revealed aescin IA and -IB and isoaescin IA and -IB as the main compounds with different functional activities. Aescin IA had the lowest IC50, the highest CC50, and an SI of > 4.6.

Keywords

Aescin - Aesculus hippocastanum - Sapindaceae - Herpes simplex virus - HSV-1 - membrane fusion - plaque reduction - triterpene saponins

Supporting Information



Publication History

Received: 26 July 2024

Accepted after revision: 01 October 2024

Article published online:
23 October 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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