Identification of a dibenzocyclooctadiene lignan as a HIV-1 non-nucleoside reverse transcriptase inhibitor.

BACKGROUND

Due to resistance to all classes of anti-HIV drugs and drug toxicity, there is a need for the discovery and development of new anti-HIV drugs.

METHODS

HIV-1 inhibitors were identified and biologically characterized for mechanism of action.

RESULTS

We identified a dibenzocyclooctadiene lignan, termed HDS2 that possessed anti-HIV activity against a wide variety of viral strains with EC50 values in the 1-3 µM range. HDS2 was shown to act as an NNRTI by qPCR and in vitro enzyme assays.

CONCLUSIONS

This compound provides a new scaffold for further optimization of activity through structure-guided design.