ANTIVIRAL AGENTS - CHARACTERISTIC ACTIVITY SPECTRUM DEPENDING ON THE MOLECULAR TARGET WITH WHICH THEY INTERACT

This chapter proposes a theory based on experience with different classes of antiviral compounds, that a detailed analysis of the antiviral activity spectrum of a given compound may often allow one to deduce its mechanism of action and to identify the molecular target of its intervention. Depending on the target protein with which they interact, antiviral agents exhibit a characteristic activity spectrum. Based on the difference in spectrum of antiviral activity and target of antiviral action, antiviral agents are divided into several distinct classes. Comparison of the activity spectrum of a novel compound with the activity spectrum of known antiviral agents for which the target of action has been established should enable to deduce the mechanism of action of this compound and pinpoint its target of action. Whether a compound interacts with a viral or cellular target protein has several consequences. First, the specificity achieved by compounds that interact with a cellular enzyme may not be as high as for compounds interacting with a viral enzyme. Second, the selectivity of antiviral compounds targeted at a cellular enzyme may also be lower than for the compounds targeted at a viral enzyme, but despite the fact that compounds interacting with a cellular target enzyme may be highly cytostatic to rapidly growing cells, they are relatively nontoxic to stationary cells, where they are able to block virus replication at concentrations well below the cytotoxicity threshold. Third, antiviral compounds that specifically interact with a viral enzyme are more likely to elicit virus drug resistance than antiviral compounds targeted at the host cell machinery. © 1993 Academic Press Inc.