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Two new anti-herpes drugs tested


Two new anti-herpes drugs have been tested in mice and appear ready for clinical trials in humans. The drugs are the first new classes of pharmaceuticals for treating herpes since the introduction of acyclovir in the 1970s. The new compounds appear to be more potent than acyclovir, and may help in cases where the virus is resistant to acyclovir.

Detail from mechanism of DNA synthesis inhibition by acyclovir and the new drugs. View full

All three drugs prevent the herpes simplex virus (HSV) from synthesizing its DNA, but the new compounds target different molecules than acyclovir. They inhibit a complex of three proteins, called the helicase-primase enzyme complex, which plays a key role in DNA synthesis. Acyclovir (whose trade name is Zovirax) blocks the polymerase enzyme.

"In animal models of HSV infection, the new drugs appear to have therapeutic value rivaling or exceeding that of acyclovir," write Clyde S. Crumpacker and Priscilla A. Schaffer of Harvard Medical School in Boston, Massachusetts in a News and Views piece accompanying the two papers in Nature Medicine. "Carefully controlled clinical trials in humans are clearly the next step for both classes of compounds."

In the first drug study, Gerald Kleymann and colleagues at Bayer AG in Wuppertal, Germany, found that a compound called BAY 57-1293 accelerates the healing of herpes lesions in mice and reduces the severity and frequency of recurrent disease.

In a similar study, James Crute, of Boehringer Ingelheim Pharmaceuticals in Ridgefield, Connecticut, and colleagues found that another compound called BILS 179 BS is highly effective against skin and vaginal herpes lesions in a mouse model of the disease.

Herpes simplex virus types 1 and 2 are responsible for the cold sores and genital herpes that have plagued humanity for centuries. Despite the availability of acyclovir therapy, the herpes simplex virus can cause life-threatening infections such as herpes encephalitis. Neither acyclovir nor the new drugs can eliminate the virus in the latent state.

"Consequently, continuation of the HSV pandemic is anticipated and efforts to develop vaccines and novel therapies aimed at eliminating latent virus are still warranted," Crumpacker and Schaffer write.

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Crumpacker, C.S. & Schaffer, P.A. New anti-HSV therapeutics target the helicase-primase complex. Nat Med 8, 327-328 (April 2002).
Crute, J.J. et al. Herpes simplex virus helicase-primase inhibitors are active in animal models of human disease. Nat Med 8, 386-391 (April 2002).
Kleymann, G. et al. New helicase-primase inhibitors as drug candidates for the treatment of herpes simplex disease. Nat Med 8, 392-398 (April 2002).

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