Peptide inhibitors against herpes simplex virus infections

Abstract

Herpes simplex virus (HSV) is a significant human pathogen causing mucocutaneous lesions primarily in the oral or genital mucosa. Although acyclovir (ACV) and related nucleoside analogs provide successful treatment, HSV remains highly prevalent worldwide and is a major cofactor for the spread of human immunodeficiency virus. Encephalitis, meningitis, and blinding keratitis are among the most severe diseases caused by HSV. ACV resistance poses an important problem for immunocompromised patients and highlights the need for new safe and effective agents; therefore, the development of novel strategies to eradicate HSV is a global public health priority. Despite the continued global epidemic of HSV and extensive research, there have been few major breakthroughs in the treatment or prevention of the virus since the introduction of ACV in the 1980s. A therapeutic strategy at the moment not fully addressed is the use of small peptide molecules. These can be either modeled on viral proteins or derived from antimicrobial peptides. Any peptide that interrupts protein-protein or viral protein-host cell membrane interactions is potentially a novel antiviral drug and may be a useful tool for elucidating the mechanisms of viral entry. This review summarizes current knowledge and strategies in the development of synthetic and natural peptides to inhibit HSV infectivity.

Inhibition of equine arteritis virus by an antimicrobial peptide produced by Bacillus sp. P34

“…Considering that treatment with AMPs is potentially effective and non-toxic to humans and animals, it has already been proposed as an alternative for disease control (Galdiero et al, 2013). According to Al-Khayat and Ahmad (2012) if TI is one or less, the drug has significant side effects, but if the index is larger than one, the margin of safety is large.…”

Activity of the antimicrobial peptide P34 against bovine alphaherpesvirus type 1

“…Resistance of human herpesviruses (HHV) to acyclovir has been widely reported and cidofovir and foscarnet -the other two drugs usually used for HHV therapy -are both nephrotoxic and their use restricted to confirmed cases of acyclovir resistance (GALDIERO et al, 2013).…”

“…Particularly, antimicrobial peptides can exert a broad spectrum of activity on infectious agents; they can be highly specific and effective and even biodegraded by peptidases, which limit their accumulation and results in lower toxicity (GALDIERO et al, 2013). Several reports have shown the antiviral potential of synthetic and naturally occurring peptides against different viruses such as HHV-1 and HHV-2, human immunodeficiency virus (HIV), vesicular stomatitis virus (VSV), influenza A virus, cytomegalovirus, adenovirus, rotavirus and other viruses (DAHER et al, 1986;CARRIEL-GOMES et al, 2007;BASU et al, 2009).…”

Rapid Screening by Cell-Based Fusion Assay for Identifying Novel Antivirals of Glycoprotein B-Mediated Herpes Simplex Virus Type 1 Infection

“…10,11) In addition, n-docosanol (Abreva) is another fusion inhibitor that has been approved by the Food and Drug Administration (FDA) and marketed for the treatment of recurrent herpes simplex labialis. 12,13) In recent years, it has also been shown that antimicrobial peptides (AMP), 14) or other synthetic peptides that bind to 3-OS HS exhibited anti-HSV-1 effects during HSV-1 infection in vivo. 15,16) The use of peptides has several advantages compared with chemical compounds; they can exert a broad spectrum of activity on different microorganisms, and they are highly specific and effective.…”