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1.
Invest Ophthalmol Vis Sci ; 54(2): 1070-9, 2013 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-23341013

RESUMO

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°, in a murine herpes simplex type 1 (HSV-1) keratitis model. METHODS: the efficacy of TAT-CD° 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-Cd° 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°, 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° is an effective antiviral against HSV-1 strain KOS when applied shortly postinfection and that aqueous-based formulations are more suitable.


Assuntos
Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Ceratite Herpética/tratamento farmacológico , Peptídeos/uso terapêutico , Animais , Chlorocebus aethiops , DNA Viral/análise , Modelos Animais de Doenças , Feminino , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Humanos , Ceratite Herpética/virologia , Camundongos , Camundongos Endogâmicos BALB C , Resultado do Tratamento
2.
Invest Ophthalmol Vis Sci ; 48(11): 5118-24, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17962464

RESUMO

PURPOSE: To test the activity of a synthetic theta-defensin, retrocyclin (RC)-2, in a murine herpes simplex virus (HSV)-1 keratitis model. METHODS: The in vitro antiviral activity of RC-2 against HSV-1 KOS was determined by yield reduction and viral inactivation assays. Efficacy in an experimental murine HSV-1 keratitis model was tested using pre- or postinfection treatment with 0.1% peptide in PBS with or without 2% methylcellulose. Viral titers in the tear film were determined by plaque assay. RESULTS: RC-2 inhibited HSV-1 KOS in vitro with an EC(50) of 10 microM (~20 microg/mL) in yield-reduction assays, but was not directly virucidal. RC-106 (a less active analogue) did not inhibit HSV-1 KOS in culture. Incubating the virus with RC-2 or applying the peptide in 2% methylcellulose to the cornea before viral infection significantly reduced the severity of ocular disease, but postinfection treatment with 0.1% RC-2 in PBS with or without 2% methylcellulose did not. Viral titers were significantly reduced on some days after infection in the preincubation and prophylaxis groups. CONCLUSIONS: RC-2 was active against HSV-1 KOS in cultures and showed protective activity in vivo when used in a prophylactic mode, but the peptide showed limited activity in a postinfection herpes keratitis model. These findings support data obtained from experiments with HIV-1, HSV-2, and influenza A, indicating that RCs inhibit the entry of viruses rather than their replication.


Assuntos
Antivirais/uso terapêutico , Defensinas/uso terapêutico , Modelos Animais de Doenças , Herpesvirus Humano 1/efeitos dos fármacos , Ceratite Herpética/prevenção & controle , Animais , Proliferação de Células/efeitos dos fármacos , Chlorocebus aethiops , Feminino , Herpesvirus Humano 1/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos Cíclicos/uso terapêutico , Células Vero/efeitos dos fármacos , Células Vero/virologia
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