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Antiviral Active Compounds Derived from Natural Sources against Herpes Simplex Viruses
Article

Peptide Inhibitor of Complement C1, RLS-0071, Reduces Zosteriform Spread of Herpes Simplex Virus Type 1 Skin Infection and Promotes Survival in Infected Mice

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Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA
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Board-Certified Dermatologist and Independent Researcher, Norfolk, VA 23507, USA
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ReAlta Life Sciences, Inc., Norfolk, VA 23502, USA
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Department of Pediatrics, Eastern Virginia Medical School, Norfolk, VA 23507, USA
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Children’s Specialty Group, 811 Redgate Avenue, Norfolk, VA 23507, USA
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Children’s Hospital of The King’s Daughters, Norfolk, VA 23507, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Barry J. Margulies
Viruses 2021, 13(8), 1422; https://doi.org/10.3390/v13081422
Received: 7 June 2021 / Revised: 16 July 2021 / Accepted: 17 July 2021 / Published: 22 July 2021
(This article belongs to the Special Issue Anti-herpesvirus Drugs and Vaccines)
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. View Full-Text
Keywords: RLS-0071; PIC1; antiviral; herpes simplex type 1; acyclovir-resistance; zosteriform infection; anti-inflammatory; complement; neutrophil; wound healing RLS-0071; PIC1; antiviral; herpes simplex type 1; acyclovir-resistance; zosteriform infection; anti-inflammatory; complement; neutrophil; wound healing
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MDPI and ACS Style

Bhutta, M.S.; Sausen, D.G.; Reed, K.M.; Gallo, E.S.; Hair, P.S.; Lassiter, B.P.; Krishna, N.K.; Cunnion, K.M.; Borenstein, R. Peptide Inhibitor of Complement C1, RLS-0071, Reduces Zosteriform Spread of Herpes Simplex Virus Type 1 Skin Infection and Promotes Survival in Infected Mice. Viruses 2021, 13, 1422. https://doi.org/10.3390/v13081422

AMA Style

Bhutta MS, Sausen DG, Reed KM, Gallo ES, Hair PS, Lassiter BP, Krishna NK, Cunnion KM, Borenstein R. Peptide Inhibitor of Complement C1, RLS-0071, Reduces Zosteriform Spread of Herpes Simplex Virus Type 1 Skin Infection and Promotes Survival in Infected Mice. Viruses. 2021; 13(8):1422. https://doi.org/10.3390/v13081422

Chicago/Turabian Style

Bhutta, Maimoona S., Daniel G. Sausen, Kirstin M. Reed, Elisa S. Gallo, Pamela S. Hair, Brittany P. Lassiter, Neel K. Krishna, Kenji M. Cunnion, and Ronen Borenstein. 2021. "Peptide Inhibitor of Complement C1, RLS-0071, Reduces Zosteriform Spread of Herpes Simplex Virus Type 1 Skin Infection and Promotes Survival in Infected Mice" Viruses 13, no. 8: 1422. https://doi.org/10.3390/v13081422

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