Evaluation of the protective effects of different antioxidants against the toxicity of herpes simplex virus 1 glycoprotein D

Herpes simplex virus type 1 (HSV-1) infects an estimated 3.8 billion people under age 50 worldwide and establishes lifelong neuronal latency, leading to recurrent disease manifestations such as neonatal and genital herpes; yet no vaccine or curative therapy exists. This study evaluated the oxidative-stress-modulating effects of HSV-1 glycoprotein D (gD) alone or in combination with two antioxidant agents - ascorbic acid and sodium selenite - in a human neuroblastoma cell line. Key oxidative-stress markers - including total glutathione (GSH), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), 8-isoprostane and protein carbonyl content - were quantified following exposure to "gD,""gD plus ascorbic acid", or "gD plus sodium selenite". Additionally, molecular docking analyses compared the binding affinities of ascorbic acid and sodium selenite for gD. Results showed that co-administration of ascorbic acid or sodium selenite with gD significantly elevated reactive oxygen species (ROS) levels compared to gD, while GSH and protein carbonyl concentrations remained unchanged. Intermediate lipid-peroxidation products did not differ significantly across treatment groups. Docking studies suggested that ascorbic acid exhibits a stronger potential for biologically relevant interaction with gD than sodium selenite, indicating a more pronounced antioxidant effect. These findings underscore the complexity of gD-induced oxidative pathways and highlight the need for further in vitro and in vivo investigations to delineate the toxicological impact of HSV-1 gD, as well as to extend analysis to other viral proteins involved in oxidative stress. © 2026 The Author(s). Published by Oxford University Press. All rights reserved.