Heli-SMACC: Helicase-targeting SMAll Molecule Compound Collection.
Holli-Joi Martin, Mohammad A Hossain, James Wellnitz, Enes Kelestemur, Joshua E Hochuli, Sumera Parveen, Cheryl Arrowsmith, Timothy M Willson, Eugene Muratov, Alexander Tropsha
Author Information
Holli-Joi Martin: UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Mohammad A Hossain: Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA. ORCID
James Wellnitz: UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Enes Kelestemur: UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Joshua E Hochuli: UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Sumera Parveen: The Structural Genomics Consortium, University of Toronto, Canada.
Cheryl Arrowsmith: The Structural Genomics Consortium, University of Toronto, Canada.
Timothy M Willson: Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA. ORCID
Eugene Muratov: UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA. ORCID
Alexander Tropsha: UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
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.
