Anti-herpetic Activity of Macrocystis pyrifera and Durvillaea antarctica Algae Extracts Against HSV-1 and HSV-2.

Estefanía Castillo,Adolfo Henríquez,Pablo A González,Cristian Agurto-Muñoz,Patricio C Smith,Diana M Álvarez,Nicolas Corrales,Luisa F Duarte,Mónica A Farías

doi:10.3389/fmicb.2020.02006

Abstract

Herpes simplex viruses (HSVs) type 1 (HSV-1) and type 2 (HSV-2) are highly prevalent in the human population, and the infections they produce are lifelong with frequent reactivations throughout life. Both viruses produce uncomfortable and sometimes painful lesions in the orofacial and genital areas, as well as herpetic gingivostomatitis, among other clinical manifestations. At present, the most common treatments against HSVs consist of nucleoside analogs that target the viral polymerases. However, such drugs are poorly effective for treating skin lesions, as they only reduce in 1–2 days the duration of the herpetic lesions. Additionally, viral isolates resistant to these drugs can emerge in immunosuppressed individuals, and second-line drugs for such variants are frequently accompanied by adverse effects requiring medical supervision. Thus, novel or improved therapeutic drugs for treating HSV lesions are needed. Here, we assessed the potential antiviral activity of aqueous extracts obtained from two brown macroalgae, namely Macrocystis pyrifera and Durvillaea antarctica against HSVs. Both extracts showed antiviral activity against acyclovir-sensitive and acyclovir-resistant HSV-1 and HSV-2. Our analyses show that there is a significant antiviral activity associated with proteins in the extract, although other compounds also seem to contribute to inhibiting the replication cycle of these viruses. Evaluation of the algae extracts as topical formulations in an animal model of HSV-1 skin infection significantly reduced the severity of the disease more than acyclovir, as well as the duration of the herpetic lesions, when compared to mock-treated animals, with the D. antarctica extract performing best. Taken together, these findings suggest that these algae extracts may be potential phytotherapeutics against HSVs and may be useful for the treatment and reduction of common herpetic manifestations in humans.

Highlights

Herpes simplex viruses (HSVs) are highly prevalent in the human population, with herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infecting approximately 70% (Looker et al, 2015) and 10% (Looker et al, 2008) of the world population, respectively
We sought to evaluate the potential antiviral properties of aqueous extracts obtained from two brown macroalgae, namely Macrocystis pyrifera and Durvillaea antarctica, against both HSV-1 and HSV-2 in a human cervix epithelial cell line (HeLa cells) and primary human gingival fibroblasts obtained from the oral cavity of healthy donors, as well as in a mouse model of HSV-1 skin infection. We found that both extracts display strong antiviral activity, some of which was significantly present in the protein fraction of the extracts suggesting that these algae extracts may have potential phytotherapeutic clinical applications for treating acyclovir-sensitive and acyclovir-resistant herpetic skin lesions
We evaluated the potential antiviral activity of aqueous extracts obtained from two brown macroalgae, namely M. pyrifera and D. antarctica, against HSV-1 and HSV-2 both, in vitro and in vivo

Summary

Introduction

Herpes simplex viruses (HSVs) are highly prevalent in the human population, with herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infecting approximately 70% (Looker et al, 2015) and 10% (Looker et al, 2008) of the world population, respectively. Valacyclovir, famciclovir, and penciclovir are nucleoside analogs commonly used for treating HSV infections (Kukhanova et al, 2014). Therapeutic oral intake of acyclovir only reduces the time to loss of the scab in approximately 2 days (from 7.9 days in the placebo group to 5.8 days in the treated group), if taken early after the onset of the prodrome or erythema symptoms (Spruance and Freeman, 1990). Due to the modest effects elicited by acyclovir and other nucleoside analogs in treating herpetic skin lesions, the benefit provided by these antiviral drugs in reducing herpetic lesions has been questioned (Kroon et al, 1990; Mindel, 1991)

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