Extracts from a wide variety of terrestrial plants, marine organisms, and microbial
isolates have been screened for anti-HIV properties using a cell-based, infectious
virus assay format. This type of phenotypic screening can identify inhibitory samples
that target virtually any step in the virus infection or replication process. Assay-guided
fractionation of active extracts has provided an array of novel, HIV inhibitory compounds
that span many different structural classes. These discoveries include new small molecule
inhibitors such as alkaloids, terpenoids, quinones, and coumarins, as well as some
larger anti-HIV peptides. Biological characterization of lead compounds revealed these
metabolites can impact critical processes such as virus entry into host cells, membrane
integrity, or reverse transcription of viral RNA. Several of these agents have undergone
extensive preclinical evaluations and one has advanced to a Phase II clinical study.
The combination of a large, diverse library of natural product samples and a new antiviral
screening platform has provided a valuable resource for discovery of novel HIV inhibitors.
