A Cationic Peptide, TAT-Cd⁰, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

Abstract

PURPOSE.To test the in vivo activity of a peptide derived from the protein transducing domain of the human immunodeficiency virus (HIV) Tat protein, TAT-Cd 0 , in a murine herpes simplex type 1 (HSV-1) keratitis model. METHODS.The efficacy of TAT-Cd 0 was assessed in a postinfection treatment model with different concentrations (1 mg/mL, 0.1 mg/mL, 0.01 mg/mL) of the peptide in one of four delivery vehicles: artificial tears, PBS, methylcellulose, and aquaphor cream. Treatment began within 4 or 24 hours postinfection. Viral titers in the tear film were determined by plaque assay. RESULTS. TAT-Cd0 reduced the severity of keratitis in all of the delivery vehicles tested when treatment started, 4 hours postinfection. Peptide in the tears or PBS delivery vehicle had the most significant reduction in disease severity and delayed the onset of vascularization and stromal keratitis. The percentage of mice presenting with disease was also significantly reduced and viral titers were reduced by 1 log at 24 hours postinfection in mice treated with 1 mg/mL TAT-Cd 0 , suggesting that inhibiting replication early is sufficient to achieve clinical effects. Lower concentrations were not effective and delaying treatment by 24 hours was also not effective.CONCLUSIONS. This study shows that TAT-Cd 0 is an effective antiviral against HSV-1 strain KOS when applied shortly postinfection and that aqueous-based formulations are more suitable. (Invest Ophthalmol Vis Sci.

Antiviral peptides as promising therapeutic drugs

“…Therefore, the knowledge of the viral genome, protein structure, replication cycle, and host cell targets is of great importance for the description of efficient inhibitors [23]. Interestingly, in some cases, a peptide designed to target a specific virus can be used as a template for the design of a new peptide against a different virus [130]. Viral surface glycoproteins are often a target, because they are essential in both the entry and penetration process, and require conformational changes given the protein-protein interaction which they undergo [23].…”

An Investigative Peptide–Acyclovir Combination to Control Herpes Simplex Virus Type 1 Ocular Infection

“…7 Studies in other laboratories have also demonstrated the antiviral potential of highly cationic peptides. Jose et al 8 have shown the efficacy of a cationic peptide, TAT-CD 0 , which is able to inhibit HSV-1 ocular infection in vivo, and Brandt et al 9 have shown the antiviral efficacy of another highly cationic molecule, a modified theta defensin, RC-2, in a murine model of HSV-1 keratitis. With our own peptide work, we suggested that coupling an agent that inhibits viral entry with a nucleoside analogue, such as ACV, that inhibits viral replication, would target the viral infection in two distinct ways.…”

Peptide Therapeutics for Treating Ocular Surface Infections

“…31 We then tested the efficacy in a mouse model of herpetic keratitis using 4 different vehicles: PBS, 2% methylcellulose gel, artificial tears, and a cream. 46 We found, regardless of the formulation, that TAT-Cd o applied topically 5 times per day at a concentration of 1 mg/mL significantly reduced the severity of corneal vascularization and stromal keratitis. Treatment reduced viral shedding by 1.5 logs at 24 h postinfection.…”