Although a large number of compounds have been identified with
antiviral activity against orthopoxviruses in tissue culture systems, it is highly preferred that these compounds have activity in vivo before they can be seriously considered for further development. One of the most commonly used animal models for the confirmation of this activity has been the use of mice infected with either
vaccinia or cowpox viruses. These model systems have the advantage that they are relatively inexpensive, readily available and do not require any special containment facilities; therefore, relatively large numbers of compounds can be evaluated in vivo for their activity. The two
antiviral agents that have progressed from preclinical studies to human safety trials for the treatment of
orthopoxvirus infections are the
cidofovir analog,
CMX001, and an inhibitor of extracellular virus formation,
ST-246. These compounds are the ones most likely to be used in the event of a bioterror attack. The purpose of this communication is to review the advantages and disadvantages of using mice infected with
vaccinia and cowpox virus as surrogate models for human
orthopoxvirus infections and to summarize the activity of
CMX001 and
ST-246 in these model
infections.