Herpes simplex virus type 1 (HSV-1) is a prevalent human pathogen primarily transmitted through skin-to-skin contact, especially on and around mucosal surfaces where there is contact with contaminated saliva during periods of viral shedding. It is estimated that 90% of adults worldwide have HSV-1
antibodies. Cutaneous HSV-1
infections are characterized by a sensation of tingling or
numbness at the initial
infection site followed by an eruption of vesicles and then painful
ulcers with crusting. These symptoms can take ten days to several weeks to heal, leading to significant morbidity. Histologically,
infections cause ballooning degeneration of keratinocytes and formation of multinucleated giant cells, ultimately resulting in a localized immune response. Commonly prescribed treatments against HSV-1
infections are
nucleoside analogs, such as
acyclovir (ACV). However, the emergence of ACV-resistant HSV (ACVR-HSV) clinical isolates has created an urgent need for the development of compounds to control symptoms of cutaneous
infections.
RLS-0071, also known as
peptide inhibitor of
complement C1 (PIC1), is a 15-amino-acid anti-inflammatory
peptide that inhibits classical complement pathway activation and modulates neutrophil activation. It has been previously shown to aid in the healing of chronic diabetic
wounds by inhibiting the excessive activation of
complement component C1 and infiltration of leukocytes. Here, we report that treatment of cutaneous
infections of HSV-1 and ACVR-HSV-1 in BALB/cJ mice with
RLS-0071 significantly reduced the rate of mortality, decreased zosteriform spread, and enhanced the healing of the
infection-associated lesions compared to control-treated animals. Therefore,
RLS-0071 may work synergistically with other
antiviral drugs to aid in wound healing of HSV-1 cutaneous
infection and may potentially aid in rapid wound healing of other pathology not limited to HSV-1.