Label-free SAMDI technology goes (anti)-viral accelerating SARS-CoV-2 drug discovery

The combination of self-assembled monolayers of alkanethiolates on gold with matrix assisted laser desorption ionization, a technique called SAMDI, has been a game changer for drug discovery. The premier label-free assay methodology, SAMDI offers key advantages for characterizing biochemical activities and binding events, including a high-throughput workflow and a label-free readout to accelerate hit finding efforts. SAMDI Tech, the exclusive provider of the SAMDI technology, combined the assay with a newly synthesized small molecule library of over a half million compounds to tackle the challenge of identifying anti-viral compounds to combat COVID-19. In this exhibitor tutorial, we discuss the advantages of the SAMDI technology over traditional technologies in the biochemical toolbox and highlight four successful SAMDI high-throughput screening campaigns for diverse therapeutic targets of SARS-CoV-2.

In a first example, the multiplexing capability of the SAMDI technology was used to screen two distinct viral proteases simultaneously, including the SARS-CoV-2 3CLpro enzyme. This screen generated twice the data in half the time, informing on compound potency and selectivity, to reveal a drug-like small molecule with anti-viral activity in cells.

In a second example, the SAMDI technology was applied to identify inhibitors of the NSP14 exonuclease activity. SARS-CoV-2 utilizes NSP14 exonuclease activity in a proofreading mechanism that not only maintains replication fidelity but also can combat many of the potential nucleotide-like drugs that are incorporated into RNA, rendering them ineffective. The flexibility of the SAMDI technology to assay metabolism of RNA substrates was key to screen hundreds of thousands of compounds to reveal novel NSP14 exonuclease inhibitors. The compounds are amongst the first NSP14 exonuclease inhibitors identified and exhibit selectivity for NSP14 over other RNA nucleases.