Concerns about possible unnatural outbreak of smallpox (such as in a bioterrorist attack), prompted a renewed interest in the search for antiviral agents that might be useful to treat smallpox (variola). Because evaluation of anti-variola compounds cannot be done in a laboratory without a BSL-4 facility, and variola (as well as monkeypox) does not cause disease in adult mice (464), routine preclinical assessment of potential anti-variola compounds can only be studied in systems using surrogate viruses, such as vaccinia and cowpox viruses.
Very recently De Clercq published an influential review article to summarize the research on vaccinia virus inhibitors in his and others' laboratories (465). The inhibitors might serve as a paradigm for the chemotherapy of poxvirus infections. According to this review, the inhibitors could generally divide into two major categories—nucleoside derivatives and non-nucleoside organic molecules.
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