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Helicase Inhibitor Pritelivir Shows Promise Against Genital Herpes


Pritelivir, a helicase inhibitor that interferes with viral replication, reduced the rate of herpes simplex virus type 2 (HSV-2) genital shedding, which has the potential to reduce sexual transmission, according to a small study described in the January 16, 2014, New England Journal of Medicine.

Anna Wald from the University of Washington in Seattle and colleagues evaluated the safety and efficacy of pritelivir versus placebo in HSV-2 positive individuals with no other major health concerns.

Pritelivir blocks the action of the viral helicase enzyme, which plays a key role in unpackaging viral genes and allowing them to be transcribed to produce new virus. Pritelivir demonstrated antiviral activity against HSV-1 and HSV-2 in prior in vitro and animal studies, the researchers noted as background. Currently approved herpes simplex dugs, including valacyclovir (Valtrex) and famciclovir (Famvir) are nucleoside analogs that interfere with the viral polymerase enzyme.

This double-blind proof-of-concept study included a total of 156 HSV-2 positive participants with a history of genital herpes outbreaks. They were randomly assigned to receive pritelivir at doses of 5, 25, or 75 mg daily, or 400 mg once-weekly, or else placebo for 28 days. They collected daily genital swabs that were PCR tested to detect the virus. 

The primary endpoint was the likelihood of genital HSV shedding during follow-up. Study findings were presented in part at the 19th Meeting of the International Society for Sexually Transmitted Diseases Research in Quebec and at the 36th International Herpesvirus Workshop in Gdansk, both in July 2011. 


  • Participants who received the higher doses of pritelivir were less likely to have detectable HSV-2 compared with placebo recipients:

o   Placebo: HSV-2 shedding on 16.6% of days;

o   5 mg daily pritelivir: 18.2% of days;

o   25 mg daily pritelivir: 9.3% of days;

o   75 mg daily pritelivir: 2.1% of days;

o   400 mg weekly pritelivir: 5.3% of days.

  • The relative risk of viral shedding compared with placebo was 1.11 (essentially no difference) with the 5 mg daily dose, 0.57 (43% lower) with the 25 mg daily dose, 0.13 (87% lower) with the 75 mg daily dose, and 0.32 (68% lower) with the 400 mg weekly dose.
  • The percentage of days with genital lesions was also significantly lower among higher-dose pritelivir recipients: 1.2% of days for participants taking either 75 mg daily or 400 mg weekly pritelivir vs 9.0% of those taking placebo (relative risk 0.13, or 87% lower).
  • The rate of adverse events was similar in all groups.

Based on these findings, the study authors concluded, "Pritelivir reduced the rates of genital HSV shedding and days with lesions in a dose-dependent manner in otherwise healthy men and women with genital herpes."

In an accompanying editorial Richard Whitley and Mark Prichard from the University of Alabama at Birmingham noted that pritelivir represents a promising option for people with drug-resistant HSV and potentially for use in combination therapy combining drugs that work by different mechanisms.

However, the U.S. Food and Drug Administration (FDA) has placed a hold on pritelivir due to signals of skin and hematological toxicity in monkeys given up to 900 times the doses tested in humans. Further investigation of the mechanisms underlying these toxicities is underway.



A Wald, L Corey, B Timmler, et al. Helicase-Primase Inhibitor Pritelivir for HSV-2 Infection. New England Journal of Medicine 370(3):201-210. January 16, 2014. 

RJ Whitley and M Prichard. A Novel Potential Therapy for HSV (Editorial). New England Journal of Medicine 370(3):273-274. January 16, 2014.