A dual controllability analysis of influenza virus-host protein-protein interaction networks for antiviral drug target discovery

Ackerman, Emily E.; Alcorn, John F.; Hase, Takeshi; Shoemaker, Jason E.

Similarly, both sets of controllability results demonstrate that driver proteins play interesting roles in the network control structure. The large population of dispensable driver proteins (robust controllability: N D ′ < N D , Table 2 ) signifies that the majority of driver proteins are making it more difficult to control the network by requiring more external inputs to control system behavior. In their absence, the number of driver proteins would decrease and it would theoretically be easier for a viral attack to compromise the network control structure. As such, a possible strategy for drug development could be to protect these proteins from repression effects during infection. Over 75% of driver proteins are classified as intermittent (global controllability: sometimes a driver protein, Table 3 ), meaning there is at least one MIS where these driver proteins are not drivers, and receive control influence through internal propagation. This lends itself to the idea of viral escape routes: under pressure, virus proteins could utilize alternative pathways to maintain system control and reach the goal of hijacking cellular function.