Exploring the antiviral potency of synthetic Cationic lipo-oligopeptides (CLOPs) against Herpes simplex virus type 1 2310162

Abstract Introduction Herpes simplex virus type 1 (HSV-1) is a common human pathogen that can infect sensory neurons and establish latency, where it remains dormant and shielded from the host’s immune defenses and the effects of antiviral drugs. To worsen this situation, prolonged use of current antiviral drugs may induce resistance. Hence, there is a need for alternative treatments to manage HSV-1 infections. In our study, we evaluated the antiviral potency of proprietary synthetic Cationic lipo-oligopeptides (CLOPs) against HSV-1. We hypothesized that CLOPs would inhibit the activity of the HSV-1 strain (F) either by disrupting its membrane envelope or by inducing endogenous mediators. Methods We utilized the TaqMan quantitative polymerase chain reaction and screened a range of non-toxic concentrations (12.5-100 µg/mL) of CLOPs for their antiviral effects on HSV-1. We also evaluated the impact of CLOPs on HSV-1-induced inflammatory responses using the Enzyme-Linked Immunosorbent Assay. Additionally, we evaluated the CLOPs’ effects on HSV-1 plaque-forming efficiency and the expression of glycoproteins D & B using the plaque reduction assay and immunofluorescence assay techniques, respectively. Results Our results showed that CLOPs (OB1111 and TP359) substantially reduced the viral load of HSV-1 in HaCaT cells. CLOPs exhibited anti-inflammatory effects by successfully reducing the production of IL-6 in HaCaT cells exposed to HSV-1. The plaque reduction assay demonstrated that CLOPs inhibited HSV-1 plaque-forming ability and altered the morphology of the plaques in Vero cells, with OB1111 and TP359 exhibiting the maximum inhibition observed. We also observed reduced expression of HSV-1 glycoproteins D & B, as well as cytopathic effects, in Vero cells following OB1111 treatment. Conclusion These findings support the potential of select CLOPs as promising therapeutic candidates for managing HSV-1 infection. Research is underway to investigate the mechanisms of the observed antiviral activity of CLOPs in HaCaT cells. Funding Source This research was supported by the National Science Foundation (NSF) HBCU-UP (HRD-1911660) grant and the Ph.D. Program in Microbiology at Alabama State University Topic Categories Vaccines and Immunotherapy (VAC)