By Nathan Seppa
Viruses survive by gaining entry into cells and then commandeering molecular machinery there to reproduce them. When released, these viral copies infect other cells, spreading the infection. In the May Chemistry & Biology, scientists working with the herpes simplex virus (HSV) report that they’ve found a compound that interferes with the interaction of two viral proteins within an infected cell, thereby preventing the virus from replicating.
Researchers at Harvard Medical School in Boston set out to find a molecule that would obstruct the contact points between Pol and UL42—two proteins essential to HSV replication. After screening a chemical library of 16,320 compounds, the scientists identified nine candidates. Further lab tests revealed that a small molecule dubbed BP5 inhibited Pol and UL42 from binding cleanly, a disruption that stopped an HSV enzyme from synthesizing long chains of viral DNA—a necessary step in replication.
BP5 was toxic to the monkey cells used in the experiment, so it wouldn’t qualify as a drug candidate, says study coauthor Donald M. Coen, a molecular biologist. However, BP5 derivatives that are less toxic might work, he says.
The work bolsters recent findings indicating that small molecules can sabotage protein-to-protein connections important to infectious agents. Such connections had previously been considered poor drug targets because they typically involve large surfaces. Scientists had thought that small-molecule drugs wouldn’t affect enough of such an interface to completely disrupt the proteins’ interactions, Coen says.
