{"id":2336,"date":"2018-10-12T08:24:20","date_gmt":"2018-10-12T08:24:20","guid":{"rendered":"https:\/\/www.mybiosource.com\/learn\/?p=2336"},"modified":"2024-04-04T08:19:03","modified_gmt":"2024-04-04T08:19:03","slug":"std-series-herpes-drugs-on-the-horizon","status":"publish","type":"post","link":"https:\/\/www.mybiosource.com\/learn\/std-series-herpes-drugs-on-the-horizon\/","title":{"rendered":"STD Series: Herpes Drugs on the Horizon"},"content":{"rendered":"

Table of Contents<\/strong><\/span><\/h2>\n

1. Introduction<\/strong>
\n2. Herpes Simplex Virus (HSV) Infections<\/strong>
\n3. Drugs for HSV Infection<\/strong>
\n4. Vaccines for HSV-2 Infection<\/strong>
\n5. Topical Microbicides for HSV-2 Infection<\/strong>
\n6. RNA Interference (RNAi) as a Treatment for HSV-2 Infection<\/strong>
\n7. Pritelivir – A Promising Treatment for HSV-2<\/strong>
\n8. Conclusion<\/strong><\/p>\n

\n

Even if HSV<\/span> infections are often subclinical, their incidence and severity have increased over the past decades due to the increasing number of immunocompromised patients with genital herpes<\/span> infection becoming one of the world\u2019s most prevalent sexually transmitted infections<\/span>. Eleven drugs have been approved to treat\u00a0 HSV<\/span> infection. Despite an increased level of understanding of the disease a prophylactic vaccine is unavailable. Several vaccines for HSV<\/span>-2 are in clinical trials, but these have demonstrated limited protection.\u00a0 Topical microbicides<\/span> designed to prevent acquisition of sexually transmitted infections<\/span> are urgently needed. Nonoxynol-9, the only commercially available spermicide, damages epithelium and may enhance human immunodeficiency virus transmission. The observation that herpes<\/span> simplex virus (HSV<\/span>) and human immunodeficiency virus bind heparan sulfate<\/span> provided the rationale for the development of sulfated or sulfonated polymers as topical agents. Although several of the polymers have advanced to clinical trials, the spectrum and mechanism of anti-HSV<\/span> activity and the effects on soluble mediators of inflammation have not been evaluated. The results indicate that PRO 2000, polystyrene sulfonate, cellulose sulfate<\/span>, and polymethylene hydroquinone sulfonate inhibit HSV<\/span>\u00a0infection10,000-fold and are active against clinical isolates, including an acyclovir<\/span>-resistant variant.\u00a0\u00a0Clinical trials of SPL-7013 (VivaGel; Starpharma Holdings Ltd\/Biomecular Research Institute Ltd), a dendrimer reported to have both anti-HIV<\/span>-1 and –HSV<\/span>-2 activity, are also underway. Subunit vaccines developed for HSV<\/span>-2 have demonstrated limited efficacy, probably as a result of the inability to elicit CD8<\/span>+ T-cell. Live, replication-defective HSV<\/span>-2 is currently being evaluated as a candidate HSV<\/span>-2 vaccine. For HSV<\/span>-2 infection, the primary cellular targets are epithelial and neuronal cells, and topically applied siRNAs have been observed in the epithelium. Whether neurons also take up siRNAs is unknown and, as HSV<\/span>-2 establishes latency in these cells, neuronal siRNA uptake could be useful for eradicating an established HSV<\/span> infection by reactivating latent virus. For example, latent virus may be reactivated by reducing the expression<\/span> of the latency-associated transcript (LAT), the only viral gene abundantly expressed during latency. The activated virus could then be cleared either with viral-specific siRNAs or conventional antiviral<\/span> drugs. RNA<\/span> interference (RNAi) provides effective antiviral<\/span> defence in plants and other organisms, several studies have focused on harnessing RNAi to inhibit viral infections. One study showed that vaginal instillation of small interfering RNAs (siRNAs) targeting HSV<\/span>-2 protected mice from lethal infection. siRNAs mixed with lipid are efficiently taken up by epithelial and lamina propria cells and silence gene expression<\/span> in the mouse vagina and ectocervix for at least nine days. Intravaginal application of siRNAs targeting the HSV<\/span>-2 UL27 and UL29 genes (which encode an envelope glycoprotein and a DNA binding protein6, respectively) was well tolerated, did not induce interferon-responsive genes or cause inflammation, and protected mice when administered before and\/or after lethal HSV<\/span>-2 challenge. These results suggest that siRNAs are attractive candidates for the active component of a microbicide designed to prevent viral infection or transmission. In a recent trial one of the most promising treatments for the herpes<\/span> simplex virus 2 (HSV<\/span>-2) in two decades, pritelivir has demonstrated that it provides greater viral suppression than the present standard treatment, valacyclovir<\/span>. In this study, conducted by a research team led by Anna Wald, MD, medical director of virology research at the University of Washington, Fred Hutchinson Cancer Research Center in Seattle<\/em>, patients who took pritelivir not only experienced less HSV<\/span> shedding than those who took valacyclovir<\/span> (2.4% vs. 5.3%), but they also had fewer lesions (1.9% vs. 3.9%), less pain, and fewer treatment-emergent adverse events (62% vs. 69%). Pritelivir, which is still in the relatively early stages of development, is particularly attractive to patients with HSV<\/span>-2 (otherwise known as genital herpes<\/span>) because it not only limits their symptoms, but also appears to reduce the likelihood of passing the infection on to a susceptible partner. Of note: pritelivir did not completely eliminate viral shedding; practitioners and patients must remember that the protection is only partial. Given that many infected individuals often do not show signs of infection but still shed viral cells intermittently, \u201cmanagement of genital HSV<\/span> should address the chronic nature of the disease rather than focusing solely on treatment of acute episodes of genital lesions,\u201d a CDC spokesperson also\u00a0noted The spokesperson added that HSV<\/span>-2 infections tend to have \u201cmuch more frequent\u201d recurrences and shedding. In the double-blind study, Dr. Wald and her team studied 91 adults\u2014who reported having had between four and nine annual genital HSV<\/span>-2 recurrences\u2014randomized into two groups. One group received pritelivir for 28 days, followed by a 28-day \u201cwashout\u201d period, and then received valacyclovir<\/span> for 28 days. The second group received valacyclovir<\/span> first, and then the 28-day washout period, followed by pritelivir. The study was terminated before all subjects had completed the entire treatment period for both drugs due to the US Food and Drug Administration<\/span> (FDA) putting a hold on the drug\u2019s clinical use because of skin and blood abnormalities that had presented in a concurrent animal trial. Dr. Wald noted that there have been no serious side effects in humans so far, and German drug maker AiCuris is working with the FDA to partially lift the hold so that patients who are resistant to drugs in the \u201cstandard treatment family,\u201d\u2014which includes the drugs acyclovir<\/span>, famciclovir, and valacyclovir<\/span>\u2014could participate in a new clinical trial. At the time of termination, 56 patients had completed both treatments. As researchers are testing and developing new treatments for herpes<\/span> infections, the US Preventive Services Task Force (USPSTF) has called for\u00a0less routine testing\u00a0for the infection because \u201cthe potential harms of screening outweigh the benefits.\u201d Because \u201cblood test screening for genital herpes<\/span> is highly inaccurate and there is no cure, so screening, early identification and treatment are unlikely to affect the course of the disease.\u201d With this in mind, novel effective treatments for the infection are that much more important to ensure the population remains safe.<\/p>\n

References<\/strong><\/p>\n

    \n
  1. Terlizzi ME1, Occhipinti A2, Luganini A3, Maffei ME4, Gribaudo G5. Dudek T, Knipe DM. Inhibition of herpes<\/span> simplex type 1 and type 2 infections by Oximacro(\u00ae), a cranberry extract with a high content of A-type proanthocyanidins (PACs-A). Antiviral<\/span> Res. 2016 Aug;132:154-64.<\/li>\n<\/ol>\n
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      1. Rupp R, Rosenthal SL, Stanberry LR. VivaGel (SPL7013 gel): A candidate dendrimer-microbicide for the prevention of HIV<\/span> and HSV<\/span> infection.\u00a0Int J Nanomedicine.\u00a02007;2(4):561\u2013566.<\/li>\n<\/ol>\n
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          1. Palliser D, Chowdhury D, Wang QY, Lee SJ, Bronson RT, Knipe DM, Lieberman J. An siRNA-based microbicide protects mice from lethal herpes<\/span> simplex virus 2 infection. Nature. 2006 Jan 5;439(7072):89-94. Epub 2005 Nov 23.<\/li>\n<\/ol>\n
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            1. Woodrow KA, Cu Y, Booth CJ, Saucier-Sawyer JK, Wood MJ, Saltzman WM. Intravaginal gene silencing using biodegradable polymer nanoparticles<\/span> densely loaded with small-interfering RNA<\/span>.\u00a0Nat Mater.\u00a02009;8(6):526\u2013533.<\/li>\n<\/ol>\n
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                 <\/p>\n","protected":false},"excerpt":{"rendered":"

                Table of Contents 1. Introduction 2. Herpes Simplex Virus (HSV) Infections 3. Drugs for HSV Infection 4. Vaccines for HSV-2 Infection 5. Topical Microbicides for HSV-2 Infection 6. RNA Interference (RNAi) as a Treatment for HSV-2 Infection 7. Pritelivir – A Promising Treatment for HSV-2 8. Conclusion Even if HSV infections are often subclinical, their […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"off","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"categories":[31],"tags":[],"class_list":["post-2336","post","type-post","status-publish","format-standard","hentry","category-news"],"_links":{"self":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/posts\/2336","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/comments?post=2336"}],"version-history":[{"count":3,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/posts\/2336\/revisions"}],"predecessor-version":[{"id":9332,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/posts\/2336\/revisions\/9332"}],"wp:attachment":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/media?parent=2336"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/categories?post=2336"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/tags?post=2336"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}