The Story So Far

Current status

This project has reached step 4 in the AViDD hit confirmation cascade.

Library selection and initial hit identification

Library

For this series we used the Small Molecule Antiviral Compound Collection (SMACC) library which is mined from the ChEMBL database. The SMACC library is a focused library that contains about 32,500 entries from the 2.4 million ChEMBL database, and the compounds have been specifically selected because they interact with viral targets. The SMACC library, and the conditions used to establish it, is described in a recent publication by Martin et al.

From the SMACC library, compounds active against Flaviviruses were selected, generating a focused library of approximately 2,000 compounds. This curated library was further diluted by the following criteria:

Selectivity for DENV over other Flaviviruses
Proper assay annotation in the original data
The STOPLIGHT calculator
Chemical clustering (selecting only one representative compound from each cluster)
Additional manual inspection
Commercial availability and cost

This generated a list of 73 compounds that were purchased and tested.

Screening

The selected compounds were screened in a phenotypic assay (DENV2 and DENV4) resulting in 10 compounds that were active at 1 µL, and 50 compounds that showed activity at 10 µL. The library was also screened in a DENV2 Rdrp picogreen assay.