Current Opinion in Investigational Drugs
A new form of antiviral clinical therapy is proposed in which three different drugs are administered against three different targets on the same virus-coded protein. If the physiological functions of the three different target sites are not independent of each other, then a mutation conferring drug resistance at one site may alter the physiological functions at the other sites and further drug resistance may not arise. The adenovirus proteinase, with its two cofactors that act synergistically on enzyme activity, may be a good model system within which to test the efficacy of this form of combination therapy.
Mangel, W.F., Brown, M.T., Baniecki, M.L., Barnard, D.L., and McGrath, W.J. 2001. Prevention of viral drug resistance by novel combination therapy. Current Opinion in Investigational Drugs 2: 613-616. PMID: 11569932