The identification of agents that can either treat or halt the spread of smallpox or other diseases caused by orthopox viruses would have great benefit in mitigating the risk of the orthopox virus being used as a biological weapon. Furthermore such agents would be useful as a therapeutic for accidental exposure to other orthopox viruses such as the recently publicized cases of monkey pox caused by human exposure to exotic imported animals. The ideal therapeutic would be an effective and safe orally available small molecule that could be taken by individuals who were exposed to an orthopox virus or had active disease. Recent evidence suggests that the proteolytic activity of a novel protease encoded by the orthopox virus genome is an obligatory event for viral proliferation. Using a proprietary process of drug discovery called TTP Translational Technology TM that combines novel medicinal chemistry with computer modeling and a series of in vitro biological screening assays, TransTech Pharma proposes to discover small molecule inhibitors of the orthopox protease that have drug like characteristics in terms of potency, safety and pharmacokinetic characteristics as a first step in developing a therapeutic anti-viral for the treatment of infections caused by the orthopox virus.