Use of pritelivir in refractory aciclovir-resistant herpes simplex virus type 2

Cannon, Luke; Tholouli, Eleni; Ward, Chris; Farooq, Hamzah Z.; Kingston, Margaret

doi:10.1177/09564624211006568

Cited by 21 publications

(26 citation statements)

References 7 publications

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“…A recent case report concerns an immunosuppressed (HIV negative) allogenic peripheral blood stem cell transplant recipient with acyclovir-resistant HSV-2 infection, which was refractory to second-line therapy (infusions with foscarnet and cidofovir with oral probenecid). Treatment with pritelivir provided symptomatic control for the duration of its use, turning PCR assays of genital swabs negative . Another recent article reported multiple successful treatment courses with pritelivir in two patients who developed acyclovir-resistant genital HSV-2 infection after hematopoietic stem cell transplantation …”

Section: Discussionmentioning

confidence: 99%

“…Treatment with pritelivir provided symptomatic control for the duration of its use, turning PCR assays of genital swabs negative. 68 Another recent article reported multiple successful treatment courses with pritelivir in two patients who developed acyclovir-resistant genital HSV-2 infection after hematopoietic stem cell transplantation. 69 Growing experience with pritelivir might lead to expansion of its indications and modes of use in the future.…”

Section: Resistancementioning

confidence: 99%

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Discovery, Chemistry, and Preclinical Development of Pritelivir, a Novel Treatment Option for Acyclovir-Resistant Herpes Simplex Virus Infections

et al. 2022

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When the nucleoside analogue acyclovir was introduced in the early 1980s, it presented a game-changing treatment modality for herpes simplex virus infections. Since then, work has been ongoing to improve the weaknesses that have now been identified: a narrow time window for therapeutic success, resistance in immunocompromised patients, little influence on frequency of recurrences, relatively fast elimination, and poor bioavailability. The present Drug Annotation focuses on the helicase−primase inhibitor pritelivir currently in development for the treatment of acyclovir-resistant HSV infections and describes how a change of the molecular target (from viral DNA polymerase to the HSV helicase−primase complex) afforded improvement of the shortcomings of nucleoside analogs. Details are presented for the discovery process leading to the final drug candidate, the pivotal preclinical studies on mechanism of action and efficacy, and on how ongoing clinical research has been able to translate preclinical promises into clinical use.

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Section: Discussionmentioning

confidence: 99%

Section: Resistancementioning

confidence: 99%

Discovery, Chemistry, and Preclinical Development of Pritelivir, a Novel Treatment Option for Acyclovir-Resistant Herpes Simplex Virus Infections

et al. 2022

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“…Genital lesions were presented on 1.9% and 3.9% of the days in the PTV and VACV cohort, respectively [ 132 ]. Effective pritelivir therapy in recurrent genital herpes in an allogenic peripheral blood stem cell transplant recipient infected with acyclovir-resistant HSV-2 was also described [ 133 ]. PTV directly inhibits the replication of HSV, limits the intracellular viral load, and prevents the spreading of the virus into a new cell.…”

Section: Compounds With Potential Use In the Treatment Of Herpesvirus...mentioning

confidence: 99%

40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?

Majewska

Młynarczyk-Bonikowska

2022

IJMS

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Herpes simplex virus types 1 and 2 HSV1 and 2, namely varicella-zoster VZV and cytomegalovirus CMV, are among the most common pathogens worldwide. They remain in the host body for life. The course of infection with these viruses is often asymptomatic or mild and self-limiting, but in immunocompromised patients, such as solid organ or bone marrow transplant recipients, the course can be very severe or even life-threatening. Unfortunately, in the latter group, the highest percentage of infections with strains resistant to routinely used drugs is observed. On the other hand, frequent recurrences of genital herpes can be a problem even in people with normal immunity. Genital herpes also increases the risk of acquiring sexually transmitted diseases, including HIV infection and, if present in pregnant women, poses a risk to the fetus and newborn. Even more frequently than herpes simplex, congenital infections can be caused by cytomegalovirus. We present the most important anti-herpesviral agents, the mechanisms of resistance to these drugs, and the associated mutations in the viral genome. Special emphasis was placed on newly introduced drugs such as maribavir and brincidofovir. We also briefly discuss the most promising substances in preclinical testing as well as immunotherapy options and vaccines currently in use and under investigation.

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“…In HIV-negative immunosuppressed patients with refractory acyclovir-resistant HSV2, pritelivir, an oral helicase-primase inhibitor, was successfully used, paving the road towards new treatments for recalcitrant infection [ 114 ]. These clinical results are in line with some recent preclinical, mouse model findings, that showed superior effectiveness of helicase primase inhibitors when compared to the nucleoside analogs [ 115 ].…”

Section: Treatment Guidelines and Resistant Pathogensmentioning

confidence: 99%

Fascinating Molecular and Immune Escape Mechanisms in the Treatment of STIs (Syphilis, Gonorrhea, Chlamydia, and Herpes Simplex)

Scurtu

Jinga

Simionescu

2022

IJMS

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The incidence of syphilis, gonorrhea, chlamydia, and herpes simplex has increased over the last decade, despite the numerous prevention strategies. Worldwide scientists report a surge in drug-resistant infections, particularly in immunocompromised patients. Antigenic variations in syphilis enable long-term infection, but benzathine penicillin G maintains its efficiency, whereas macrolides should be recommended with caution. Mupirocin and zoliflodacin were recently introduced as therapies against ceftriaxone-resistant gonococcus, which poses a larger global threat. The gastrointestinal and prostatic potential reservoirs of Chlamydia trachomatis may represent the key towards complete eradication. Similar to syphilis, macrolides resistance has to be considered in genital chlamydiosis. Acyclovir-resistant HSV may respond to the novel helicase-primase inhibitors and topical imiquimod, particularly in HIV-positive patients. Novel drugs can overcome these challenges while nanocarriers enhance their potency, particularly in mucosal areas. This review summarizes the most recent and valuable discoveries regarding the immunopathogenic mechanisms of these sexually transmitted infections and discusses the challenges and opportunities of the novel molecules and nanomaterials.

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Use of pritelivir in refractory aciclovir-resistant herpes simplex virus type 2

Cited by 21 publications

References 7 publications

Discovery, Chemistry, and Preclinical Development of Pritelivir, a Novel Treatment Option for Acyclovir-Resistant Herpes Simplex Virus Infections

Discovery, Chemistry, and Preclinical Development of Pritelivir, a Novel Treatment Option for Acyclovir-Resistant Herpes Simplex Virus Infections

40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?

Fascinating Molecular and Immune Escape Mechanisms in the Treatment of STIs (Syphilis, Gonorrhea, Chlamydia, and Herpes Simplex)

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