In silico screening for non-nucleoside HIV-1 reverse transcriptase inhibitors using physicochemical filters and high-throughput docking followed by in vitro evaluation.

Reverse transcriptase, being the pivot in human immunodeficiency virus replication, is one of the most attractive targets for the development of new antiretroviral agents. We applied a virtual screening workflow based on a combination of physicochemical filters with high-throughput rigid molecular docking to discover novel efficient lead scaffolds for human immunodeficiency virus type 1 reverse transcriptase inhibition. In our protocol, different filters were employed to enrich the lead-likeness and improve the ligands efficiency of the filtered compounds. Out of the 238,819 compounds included in the National Cancer Institute database, 500 virtual screening hits were retrieved employing FILTER and FRED (molecular docking engine) softwares. Four compounds from the 20 highest ranking scored hits tested positive in human immunodeficiency virus type 1 reverse transcriptase using non-radioactive colorimetric assay method. These results demonstrate that our virtual screening protocol is able to enrich novel scaffolds for human immunodeficiency virus type 1 reverse transcriptase inhibition that could be useful for drug development in the area of acquired immune-deficiency syndrome treatment.