TY - JOUR
T1 - An immunomodulating dipeptide, SCV-07, is a potential therapeutic for recurrent genital herpes simplex virus type 2 (HSV-2)
AU - Rose, William A.
AU - Tuthill, Cynthia
AU - Pyles, Richard B.
N1 - Funding Information:
Funding : This research was sponsored by SciClone Pharmaceuticals, Inc. (Foster City, CA). WAR and RBP were supported by the Gulf South STI/Topical Microbicides Cooperative Research Center (NIAID U19 AI61972).
PY - 2008/9
Y1 - 2008/9
N2 - Herpes simplex virus type 2 (HSV-2) infections produce a recurrent disease state associated with susceptibility to other pathogens, including human immunodeficiency virus (HIV), and cannot be cured by current therapeutic treatments. The HSV-2 epidemic must therefore be addressed by therapeutic strategies that reduce recurrent lesions and ideally lack the possibility for development of drug resistance. To this end, the therapeutic potential of SCV-07 (gamma-d-glutamyl-l-tryptophan), a synthetic dipeptide with potent immunomodulatory and antimicrobial activity, was studied in the guinea pig model of recurrent genital HSV-2. Initial evaluations showed that when delivered orally, but not subcutaneously, SCV-07 significantly reduced recurrent lesions. Oral dose ranging studies indicated that, of the tested amounts, 5 μg/kg was optimal when delivered after an overnight fast. Interestingly, fasting induced a significant increase in recurrent lesions in vehicle-treated guinea pigs relative to non-fasted animals. Despite this increase, SCV-07 significantly reduced lesion formation in treated animals but showed no durability following cessation of treatment. In fact, this regimen of SCV-07 treatment produced statistically indistinguishable outcomes compared with those provided by topical aciclovir. These data illustrate that SCV-07 may provide an easily administered alternative or supplemental treatment option for genital HSV-2 recurrent disease.
AB - Herpes simplex virus type 2 (HSV-2) infections produce a recurrent disease state associated with susceptibility to other pathogens, including human immunodeficiency virus (HIV), and cannot be cured by current therapeutic treatments. The HSV-2 epidemic must therefore be addressed by therapeutic strategies that reduce recurrent lesions and ideally lack the possibility for development of drug resistance. To this end, the therapeutic potential of SCV-07 (gamma-d-glutamyl-l-tryptophan), a synthetic dipeptide with potent immunomodulatory and antimicrobial activity, was studied in the guinea pig model of recurrent genital HSV-2. Initial evaluations showed that when delivered orally, but not subcutaneously, SCV-07 significantly reduced recurrent lesions. Oral dose ranging studies indicated that, of the tested amounts, 5 μg/kg was optimal when delivered after an overnight fast. Interestingly, fasting induced a significant increase in recurrent lesions in vehicle-treated guinea pigs relative to non-fasted animals. Despite this increase, SCV-07 significantly reduced lesion formation in treated animals but showed no durability following cessation of treatment. In fact, this regimen of SCV-07 treatment produced statistically indistinguishable outcomes compared with those provided by topical aciclovir. These data illustrate that SCV-07 may provide an easily administered alternative or supplemental treatment option for genital HSV-2 recurrent disease.
KW - Guinea pig
KW - HSV-2
KW - Immunomodulating dipeptide
KW - Recurrent genital disease
KW - SCV-07
KW - Therapeutic
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U2 - 10.1016/j.ijantimicag.2008.04.010
DO - 10.1016/j.ijantimicag.2008.04.010
M3 - Article
C2 - 18619817
AN - SCOPUS:49749130822
SN - 0924-8579
VL - 32
SP - 262
EP - 266
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
IS - 3
ER -