Heli-SMACC: Helicase-targeting SMAll Molecule Compound Collection

Martin, H.-J.; Hossain, M. A.; Wellnitz, J.; Kelestemur, E.; Hochuli, J.; Perveen, S.; Arrowsmith, C.; Willson, T. M.; Muratov, E.; Tropsha, A.

doi:10.1101/2024.07.04.602122

bioRxiv · 10.1101/2024.07.04.602122

Heli-SMACC: Helicase-targeting SMAll Molecule Compound Collection

Martin, H.-J.·Hossain, M. A.·Wellnitz, J.·Kelestemur, E.·Hochuli, J.·Perveen, S.·Arrowsmith, C.·Willson, T. M.·Muratov, E.·Tropsha, A.

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Abstract

Helicases have emerged as promising targets for the development of antiviral drugs; however, the family remains largely undrugged. To support the focused development of viral helicase inhibitors we identified, collected, and integrated all chemogenomics data for all available helicases from the ChEMBL database. After thoroughly curating and enriching the data with relevant annotations we have created a derivative database of helicase inhibitors which we dubbed Heli-SMACC (Helicase-targeting SMAll Molecule Compound Collection). The current version of Heli-SMACC contains 20,432 bioactivity entries for viral, human, and bacterial helicases. We have selected 30 compounds with promising viral helicase activity and tested them in a SARS-CoV-2 NSP13 ATPase assay. Twelve compounds demonstrated ATPase inhibition and a consistent dose-response curve. The Heli-SMACC database may serve as a reference for virologists and medicinal chemists working on the development of novel helicase inhibitors. Heli-SMACC is publicly available at https://smacc.mml.unc.edu. HighlightsO_LIWe created a curated Helicase-Targeting SMAll Molecule Compound Collection (Heli-SMACC). C_LIO_LIHeli-SMACC covers 29 human, viral, and bacterial helicases. C_LIO_LITwelve of thirty selected compounds demonstrated inhibitory activity in a SARS-CoV-2 NSP13 ATPase Assay. C_LIO_LIHeli-SMACC is freely available online at https://smacc.mml.unc.edu. C_LI TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=125 SRC="FIGDIR/small/602122v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@8e098forg.highwire.dtl.DTLVardef@115cb2borg.highwire.dtl.DTLVardef@1cd9da3org.highwire.dtl.DTLVardef@2870a6_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Martin, H.-J., Hossain, M. A., Wellnitz, J., Kelestemur, E., Hochuli, J., Perveen, S., Arrowsmith, C., Willson, T. M., Muratov, E., Tropsha, A.. 2024-07-08. Heli-SMACC: Helicase-targeting SMAll Molecule Compound Collection. https://doi.org/10.1101/2024.07.04.602122

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