Compositions and methods for treating a patient infected with a metazoan parasite by inhibiting the enzymatic action of the metazoan parasite protease. The compositions comprise at least one metazoan protease inhibitor which binds to the S2 subsite and at least one of the S1 and S1' subsites of the metazoan parasite protease. The methods comprise administration to a patient infected with a metazoan parasite of at least one metazoan protease inhibitor in an amount effective to inhibit the protease of the metazoan parasite, thereby killing the parasite.