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C. R. Brandt, R. Akkarawongsa, T. Potocky, E. English, S. Gellman; In vitro and in vivo Inhibition of Herpes Simplex Virus Infection by Cationic Beta-Peptides. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4489.
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Cationic α-peptides block HSV-1 in culture and animal models. Peptides made of β-amino acids are resistant to proteases and are structurally more constrained at shorter lengths. The goal was to test cationic β-peptides in culture and a murine model of HSV keratitis.
Activity in Vero cells was tested using a β-gal expressing reporter virus (hrR3). Peptides were added at various times before and after infection to determine the step that is blocked. Toxicity was tested using MTS assays. Efficacy in vivo was tested by post-infection treatment and prophylactically by pre-treating corneas with peptide in 2% methylcellulose.
The peptides were not toxic up to 50 µM. Amongst the 3 peptides, the one with the strongest 14-helical propensity and globally amphiphilic was most active (EC50 3.0 µM). The peptides were not virucidal, did not block attachment, were not active post-infection, and did not induce cellular resistance to infection. The β-peptides inhibited entry (EC50 3.0 µM). The most active peptide was active when used before infection but was ineffective when topically applied post-infection.
Cationic β-peptides are selective inhibitors of HSV-1 entry and show in vivo efficacy similar to cationic α-peptides such as θ-defensins. Further studies of cationic β-peptides as potential antiviral agents are warranted.
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