Winding Up with New Herpes Drugs

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Science  12 Apr 2002:
Vol. 296, Issue 5566, pp. 219
DOI: 10.1126/science.296.5566.219a

Herpes simplex viruses (HSVs) cause a broad spectrum of diseases, ranging from oral and genital herpes in adults to life-threatening illness in newborn infants and immunocompromised individuals. HSV infections are typically treated with the antiviral drug acyclovir or other nucleoside analogs that act by inhibiting the viral DNA polymerase. Although these drugs are safe and very effective, they must be administered early in infection for maximal antiviral activity, and certain isolates of HSV have become resistant to the drugs. To circumvent these limitations, Crute et al. and Kleymann et al. used high-throughput screening assays to develop a new class of drugs that disrupt HSV replication through a different mechanism of action. These new drugs (amino-thiazolylphenyl-containing compounds and thiazole urea derivatives) act by inhibiting the HSV helicase-primase complex that normally unwinds the double-stranded viral DNA and generates primers for viral DNA synthesis. On the basis of promising results in rodent models—even when administered at a late stage of HSV infection—these new drugs, or optimized derivatives thereof, may soon be tested in clinical trials.—PAK

Nature Med. 8, 386; 392 (2002).

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