Key result
Captopril reduces HSV-1 viral gene expression by ~34% and attenuates cytopathic effects in neuroblastoma cells.
Why the study?
Current HSV-1 treatments face compliance and resistance issues, and the potential antiviral properties of RAAS components have not been well characterized in reference to HSV-1.
Does captopril reduce HSV-1-induced cytopathic effects and viral replication in SH-SY5Y neuroblastoma cells?
Does captopril reduce HSV-1-induced cytopathic effects and viral replication in SH-SY5Y neuroblastoma cells?
Effect estimate: 34% decrease
p-value: p=<0.0001
Captopril demonstrates antiviral properties against HSV-1 in vitro by attenuating cytopathic effects and reducing viral replication.
May support preclinical antiviral exploration of captopril; leaves open clinical relevance pending in vivo and human studies.
Background: Over 60% of the United States population is infected with herpes simplex virus 1 (HSV-1). Current HSV-1 treatment regimens exert their antiviral effects through a common mechanism of action and suffer from high dosing frequencies, which may contribute to patient noncompliance and the subsequent development of antiviral resistance. Although primarily known for their functions in maintaining homeostatic control of arterial blood and osmotic pressures, components of the Renin-Angiotensin Aldosterone System (RAAS) have been implicated in viral replication and some components demonstrated antiviral properties. However, the antiviral properties of RAAS components have not been well characterized in reference to HSV-1. Methods: To address this gap in knowledge, we evaluated the antiviral effects of captopril, an Angiotensin Converting Enzyme 1 (ACE-1) inhibitor, on HSV-1 infection in SH-SY5Y neuroblastoma cells. We demonstrated that captopril attenuates HSV-1-induced cytopathic effects (CPE) via cell-based and morphological assays. To investigate the potential mechanism, we conducted molecular modeling studies and identified the ability of captopril to interact with and bind HSV-1 glycoprotein D. To determine where in the virus life cycle captopril exerts its protective effects, we performed experiments observing the effect of captopril on both viral entry and replication utilizing a green fluorescent protein-tagged virus and subsequent quantitative Polymerase Chain Reaction. Results: Results suggest captopril protects cells from HSV-1-induced CPE through its effect on viral replication by increasing cell viability in infected cells and decreasing virus replication, which we propose is modulated through the decreased expression of ICP0. Conclusions: Collectively, the results presented here support further evaluation of captopril, and other RAAS components, as a basis for potential novel therapeutic interventions for the treatment of HSV-1, its associated pathologies, and potentially other virus infections.
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Wofford et al. (2020) studied Herpes simplex virus 1 (HSV-1) infection. Captopril vs. Vehicle control (0.1% DMSO) was evaluated on ICP0 viral gene expression (34% decrease, p=<0.0001). Captopril treatment at 10 nM attenuated HSV-1-induced cytopathic effects and decreased viral ICP0 gene expression by approximately 34% in SH-SY5Y neuroblastoma cells.
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