Newly designed small molecules can inhibit HIV replication by blocking a viral-host interaction, reports a study published online this week in Nature Chemical Biology.

Interaction between the HIV-1 enzyme, integrase, and the cellular cofactor LEDGF/p75 plays a crucial role in viral integration. Zeger Debyser and colleagues design small molecules which block this interaction and inhibit HIV replication, even with HIV strains that are resistant to clinically used integrase inhibitors.

This work demonstrates a novel mechanism for inhibiting HIV integrase, and also illustrates the feasibility for the design of small molecules that inhibit protein-protein interaction between a viral protein and a cellular host factor.