Helicase–Primase Inhibitors: A New Approach to Combat Herpes Simplex Virus and Varicella Zoster Virus

Biswas, Subhajit; Field, Hugh J.

doi:10.1002/9783527635955.ch6

“…(6). This novel non-nucleosidic inhibitor has shown excellent antiviral activity against HSV-1 and HSV-2, bovine herpesvirus and pseudorabies virus [98-100]. This compound possess the ability to inhibit the helicase primase complex encoded by HSV genes (UL5, UL52 and UL8) which results in the inhibition of viral DNA synthesis.…”

Section: New Anti-hsv Drugsmentioning

confidence: 99%

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

Vadlapudi

¹

,

Vadlapatla²,

Mitra³

2013

PRI

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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.

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“…(6). This novel non-nucleosidic inhibitor has shown excellent antiviral activity against HSV-1 and HSV-2, bovine herpesvirus and pseudorabies virus [98][99][100]. This compound possess the ability to inhibit the helicase primase complex encoded by HSV genes (UL5, UL52 and UL8) which results in the inhibition of viral DNA synthesis.…”

Section: Hsv Latent Cyclementioning

confidence: 99%

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

Vadlapudi¹,

Vadlapatla²,

Mitra³

2013

Recent Patents on Anti-Infective Drug Discovery

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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.

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The Helicase–Primase Complex as a Target for Effective Herpesvirus Antivirals

Field¹,

Mickleburgh

²

2012

Advances in Experimental Medicine and Biology

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Herpes simplex virus and varicella-zoster virus have been treated for more that half a century using nucleoside analogues. However, there is still an unmet clinical need for improved herpes antivirals. The successful compounds, acyclovir; penciclovir and their orally bioavailable prodrugs valaciclovir and famciclovir, ultimately block virus replication by inhibiting virus-specific DNA-polymerase. The helicase-primase (HP) complex offers a distinctly different target for specific inhibition of virus DNA synthesis. This review describes the synthetic programmes that have already led to two HP-inhibitors (HPI) that have commenced clinical trials in man. One of these (known as AIC 316) continues in clinical development to date. The specificity of HPI is reflected by the ability to select drug-resistant mutants. The role of HP-antiviral resistance will be considered and how the study of cross--resistance among mutants already shows subtle differences between compounds in this respect. The impact of resistance on the drug development in the clinic will also be considered. Finally, herpesvirus latency remains as the most important barrier to a therapeutic cure. Whether or not helicase primase inhibitors alone or in combination with nucleoside analogues can impact on this elusive goal remains to be seen.

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Helicase–Primase Inhibitors: A New Approach to Combat Herpes Simplex Virus and Varicella Zoster Virus

Cited by 4 publications

References 45 publications

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

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

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

The Helicase–Primase Complex as a Target for Effective Herpesvirus Antivirals

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