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.
PURPOSE: To test the activity of a synthetic theta-defensin, retrocyclin (RC)-2, in a murineherpes simplex virus (HSV)-1keratitis 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 murineHSV-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.
Authors: Neeloffer Mookherjee; Marilyn A Anderson; Henk P Haagsman; Donald J Davidson Journal: Nat Rev Drug Discov Date: 2020-02-27 Impact factor: 84.694
Authors: Lena J Al-Dujaili; Patrick P Clerkin; Christian Clement; Harris E McFerrin; Partha S Bhattacharjee; Emily D Varnell; Herbert E Kaufman; James M Hill Journal: Future Microbiol Date: 2011-08 Impact factor: 3.165
Authors: James M Hill; Ethan M Stern; Partha S Bhattacharjee; Daniel Malamud; Christian Clement; Paulo Rodriguez; Walter J Lukiw; Augusto C Ochoa; Timothy P Foster; Cruz Velasco; Harris E McFerrin Journal: Antiviral Res Date: 2013-07-13 Impact factor: 5.970