Update On Emerging Antivirals For The Management Of Herpes Simplex Virus Infections: A Patenting Perspective

Abstract

Herpes simplex virus (HSV) infections can be treated efficiently by the application of antiviral drugs. The herpes family of viruses is responsible for causing a wide variety of diseases in humans. The standard therapy for the management of such infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valaciclovir and famciclovir. Though effective, long term prophylaxis with the current drugs leads to development of drug-resistant viral isolates, particularly in immunocompromised patients. Moreover, some drugs are associated with dose-limiting toxicities which limit their further utility. Therefore, there is a need to develop new antiherpetic compounds with different mechanisms of action which will be safe and effective against emerging drug resistant viral isolates. Significant advances have been made towards the design and development of novel antiviral therapeutics during the last decade. As evident by their excellent antiviral activities, pharmaceutical companies are moving forward with several new compounds into various phases of clinical trials. This review provides an overview of structure and life cycle of HSV, progress in the development of new therapies, update on the advances in emerging therapeutics under clinical development and related recent patents for the treatment of Herpes simplex virus infections.

Herpes simplex keratitis: challenges in diagnosis and clinical management

“…Current treatment for HSK includes acyclovir, ganciclovir, triflurothymidine, penciclovir, and valacyclovir 13,36. Acyclovir and its derivatives are nucleoside analogs that are selectively phosphorylated by the virally encoded thymidine kinase to be used as a substrate by DNA polymerase; this drug is not a substrate for the host thymidine kinase, and thus has a reduced side-effect profile.…”

“…Because it affects only newly synthesized viral DNA, it does not cure infected cells of the virus, but it does prevent new viruses from being produced. Since acyclovir has poor bioavailability, high doses and increased frequency of administration are required 8,36,39,40. Valacyclovir, another nucleoside analog, has improved bioavailability, and thus it has reduced frequency of administration and can lead to better patient adherence 41.…”

“…Though it has fewer side effects, it can cause blurred vision, punctuate keratitis, and eye irritation 8,42,43. Nonetheless, long-term treatment with these nucleoside analogs has resulted in resistance, especially in immunocompromised hosts, due to mutations in thymidine kinase or in DNA polymerase, which are selected for when the immune system does not efficiently remove newly made infectious virus 5,8,36,44–46. Second-line treatment includes foscarnet and cidofovir, but they have less specificity for viral DNA and are more likely to have significant toxicity in patients.…”

In vitro antiviral activity of Brazilian Cerrado plant extracts against animal and human herpesviruses

“…The Opuntia streptacantha inhibited virus replication and inactivated extracellular virus, such as HSV, equine herpes virus, pseudorabies virus (Jassim and Naji, 2003). Bidens pilosa extract was effective against HSV-1 and HSV-2 with potent virucidal activity (Vadlapudi et al, 2013). Virucidal activity has also been described in crude hydroethanolic extract from the stem bark of S. terebinthifolia and was effective against HVS-1 in the attachment and penetration stages (Nocchi et al, 2016).…”

“…Author(s) agree that this article remain permanently open access under the terms of the Creative Commons Attribution License 4.0 International License herpesvirus is a growing problem, particularly in immunocompromised patients (Vadlapudi et al, 2013). More recently, outbreaks of equine herpesvirus have had an impact on the equine industry, and stimulated interest in antiherpetic interventions (Vissani et al, 2016).…”