acyclovir and docosanol

During the last three decades, a better understanding of viral replication and disease states caused by viral infections have led to the development of newer antiviral agents with enhanced activity and better tolerability. This review focuses on newer systemic and topical antiviral agents that are used in treatment of herpes viruses including herpes simplex type-1 (HSV-1) and type-2 (HSV-2), varicella-zoster virus (VZV) and cytomegalovirus CMV) as well as the human papilloma virus (HPV). Included in this article are the agents famciclovir, penciclovir, valganciclovir, imiquimod, docosanole and brivudin.

Topics: 2-Aminopurine; Acyclovir; Aminoquinolines; Antiviral Agents; Bromodeoxyuridine; Famciclovir; Fatty Alcohols; Ganciclovir; Guanine; Humans; Imiquimod; Valganciclovir; Virus Diseases

Topics: Acyclovir; Antiviral Agents; Clinical Trials as Topic; Fatty Alcohols; Guanine; Herpes Labialis; Humans; Ointments

Significant advances have been made in the development of effective antiherpes-virus chemotherapy in the last decades. Acyclovir was approved for the treatment of HSV infections over 15 years ago and it remains an important and reliable antiviral agent. In this review the most promising new antiviral drugs are described. It will focus on the drugs that have just entered the therapy, or will do so within a short period of time. Some of the them are still under clinical investigation. Antiviral activity, results of clinical trials and adverse effects will be presented.

Topics: Acyclovir; Animals; Antiviral Agents; Cytosine; DNA, Viral; Fatty Alcohols; Herpesviridae Infections; Humans

(1) Herpes is a contagious, recurrent viral infection of the skin and mucous membranes. In immunocompetent patients the recurrences can be troublesome but they heal spontaneously. Management is mainly based on lifestyle measures. Local application of an antiviral drug such as aciclovir has modest effects. It reduces healing time by about 2 days provided treatment is started as soon as the first symptoms appear; (2) Docosanol, a fatty alcohol, was recently authorized in France for treatment of episodes of herpes labialis; (3) A trial in 474 patients showed no tangible difference between docosanol and 5% aciclovir in reducing healing time; (4) Clinical evaluation also includes two trials versus an excipient (polyethylene glycol) including 370 and 373 patients. The median healing time was reduced by less than a day; (5) In these trials, the adverse effects of docosanol were similar to those of the excipients. In particular, docosanol cream contains excipients that can provoke allergic reactions; (6) In practice, docosanol cream is barely or no more effective than an excipient in treating acute episodes of herpes labialis. Lifestyle measures are still the cornerstone of herpes management.

Topics: Acyclovir; Antiviral Agents; Double-Blind Method; Drug Approval; Excipients; Fatty Alcohols; France; Herpes Labialis; Humans; Polyethylene Glycols; Randomized Controlled Trials as Topic; Stearic Acids

Resveratrol (3,5,4'-trihydroxystilbene) is a natural component of certain foods, such as grapes, that has been shown to have anti-herpes simplex virus (HSV) activity in vitro. To determine if it is active in vivo, the abraded epidermis of SKH1 mice were infected with HSV-1 and topically treated with 12.5 or 25% resveratrol cream or cream only. Initial studies demonstrated that: (1). 25% resveratrol cream topically applied two, three, or five times a day effectively suppressed lesion development whereas 12.5% resveratrol cream effectively suppressed lesion formation when applied five times a day starting 1h after infection; (2). when treatment was begun 1, 6, or 12h after infection, both 12.5 and 25% resveratrol were effective at 1 and 6h after infection, but not if applied 12h after infection. Comparative studies between resveratrol cream, 10% docosanol cream (Abreva) and 5% acyclovir ointment (Zovirax) were also carried out. When treatment was begun 1h after infection and repeated every 3h five times a day for 5 days, 12.5 and 25% resveratrol significantly (P=0.0001) inhibited the development of HSV-1 induced skin lesions. Acyclovir was as effective (P=0.0001) as resveratrol. Animals that were topically treated with docosanol were not protected and developed lesions in a manner indistinguishable from cream only controls. These studies were repeated with an HSV-1 acyclovir-resistant virus. As before, 12.5 and 25% resveratrol cream effectively suppressed lesion formation. The skin of resveratrol-treated animals showed no apparent dermal toxicity such as erythema, scaling, crusting, lichenification, or excoriation. These studies demonstrate that topically applied resveratrol inhibits HSV lesion formation in the skin of mice.

Topics: Acyclovir; Administration, Topical; Animals; Antiviral Agents; Drug Resistance, Viral; Fatty Alcohols; Herpes Simplex; Herpesvirus 1, Human; Mice; Mice, Hairless; Resveratrol; Stilbenes

Interactions between docosanol (n-docosanol, behenyl alcohol) and nucleoside or pyrophosphate analogs were investigated in vitro. The anti-HSV activity of acyclovir (ACV) was synergistically enhanced by treatment of cells with docosanol as judged by inhibition of progeny virus production and plaque formation. This drug interaction between ACV and docosanol was observed with laboratory strains of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), oral and genital clinical isolates of HSV, cytomegalovirus (CMV), and varicella zoster virus (VZV). Near optimal concentrations of docosanol plus ACV inhibited HSV replication >99% more than either drug alone, including emergence of ACV-resistant variants. The response was observed with African Green Monkey kidney cells, normal human foreskin cells, and normal human lung cells. Treatment of cells with docosanol also synergistically intensified the inhibition of HSV production by all tested nucleoside analogs, including trifluorothymidine (TFT), adenine arabinoside (Ara-A), and ribavirin. An additive anti-HSV effect was observed with docosanol and phosphonoformate (PFA). No evidence was found for either synergistic inhibition of cellular DNA synthesis or induction of overt cellular toxicity when docosanol was combined with ACV, TFT, Ara-A, ribavirin, PFA, 8-azaguanine, or 5-fluorouracil. The ability of docosanol treatment to increase the antiviral activities of nucleoside analog antiviral drugs, coupled with a lack of toxic interactions, translates to substantial improvements in drug selectivity ratios.

Topics: Acyclovir; Animals; Antiviral Agents; Cell Line; Chlorocebus aethiops; Cytomegalovirus; Diphosphates; Dose-Response Relationship, Drug; Drug Synergism; Fatty Alcohols; Fibroblasts; Herpesviridae; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 3, Human; Humans; Isotope Labeling; Nucleosides; Thymidine; Tritium; Vero Cells; Viral Plaque Assay; Virus Replication

Topics: Acyclovir; Antiviral Agents; Fatty Alcohols; Guanine; Herpes Labialis; Humans; Recurrence; Simplexvirus; Stomatitis, Herpetic; Virulence; Virus Activation; Virus Shedding

There are 3 new topical treatments for herpes labialis that have either been approved by the US Food and Drug Administration (penciclovir cream [Denavir] and n-docosanol cream [Abreva]) or recently undergone extensive clinical evaluation (acyclovir cream). The relative efficacy of these products is unknown.. To compare the efficacy of penciclovir cream, acyclovir cream, n-docosanol cream, and acyclovir ointment in an experimental animal model of cutaneous herpes simplex virus type 1 (HSV-1) disease.. The backs of guinea pigs were infected with HSV-1 using a vaccination instrument. Active treatments and corresponding vehicle controls were applied for 3 to 5 days beginning 24 hours after inoculation.. After completion of treatment, the animals were killed and the severity of the infection assessed from the number of lesions, the total lesion area, and the lesion virus titer.. Penciclovir cream effected modest reductions in lesion number (19%), area (38%), and virus titer (88%) compared with its vehicle control, and each of these differences was significantly greater (P<.05) than the reductions effected by acyclovir ointment (0%, 21%, and 75%, respectively). The acyclovir cream effect (reductions of 4%, 28%, and 77%, respectively) was less than that of penciclovir cream, and this difference was confirmed by 2 additional head-to-head experiments. Two experiments with n-docosanol cream failed to show statistically significant differences by any parameter between n-docasonol cream and vehicle control-treated sites or between n-docosanol and untreated infection sites.. In this model, the efficacy of penciclovir cream was greater than acyclovir cream, acyclovir cream was greater than or equal to acyclovir ointment, and acyclovir ointment was greater than n-docosanol cream. Since our model was designed to evaluate compounds that function primarily through antiviral activity, the negative findings with n-docosanol in these studies do not exclude that it might work clinically through other mechanisms.

Topics: Acyclovir; Administration, Topical; Animals; Disease Models, Animal; Fatty Alcohols; Female; Guanine; Guinea Pigs; Herpes Labialis; Herpesvirus 1, Human; Humans; Treatment Outcome

Topics: Acyclovir; Administration, Topical; Animals; Antiviral Agents; Disease Models, Animal; Fatty Alcohols; Guanine; Guinea Pigs; Herpes Labialis; Humans; Ointments; Treatment Outcome

This article reports that 1-docosanol, a 22-carbon-long saturated alcohol, exerts a substantial inhibitory effect on replication of certain viruses (e.g., herpes simplex virus and respiratory syncytial virus) within primary target cells in vitro. To study the basis for its viral inhibitory activity, a suspension of 1-docosanol was formulated in an inert and nontoxic surfactant, Pluronic F-68; this suspension exerted potent inhibitory activity on the ability of susceptible viruses to infect cultured target cells. Susceptible viruses included wild-type herpes simplex viruses 1 and 2 as well as acyclovir-resistant herpes simplex virus 2 and also respiratory syncytial virus--all of which are lipid-enveloped. In contrast, nonenveloped poliovirus was not susceptible to the inhibitory action of 1-docosanol. Although the precise mechanism has yet to be defined, current evidence suggests that 1-docosanol inhibits viral replication by interfering with the early intracellular events surrounding viral entry into target cells. It is possible that interaction between the highly lipophilic compound and components of target cell membranes renders such target cells less susceptible to viral fusion and/or entry. If this mechanism proves to be correct, 1-docosanol may provide a broad spectrum activity against many different viruses, especially those with lipid-containing envelopes.

Topics: Acyclovir; Animals; Antigens, Viral; Antiviral Agents; Drug Resistance, Microbial; Fatty Alcohols; Kinetics; Lipids; Poliovirus; Simplexvirus; Vero Cells; Viral Plaque Assay; Virus Replication