Biological and Medicinal Chemistry

Tuaimenal A, a Meroterpene from the Irish Deep-Sea Soft Coral Duva florida, Displays Inhibition of the SARS-CoV-2 3CLpro Enzyme.

Authors

  • Nicole E. Avalon Department of Chemistry, University of South Florida, Tampa, FL, USA. ,
  • Jordan Nafie BioTools, Inc., Jupiter, FL, USA. ,
  • Carolina De Marco Verissimo Molecular Parasitology Laboratory (MPL), Centre for One Health and Ryan Institute, School of Natural Science, National University of Ireland Galway, Galway, Republic of Ireland. ,
  • Luke C. Warrensford Department of Chemistry, University of South Florida, Tampa, FL, USA. ,
  • Sarah G. Dietrick Department of Chemistry, University of South Florida, Tampa, FL, USA. ,
  • Amanda R. Pittman Department of Chemistry, University of South Florida, Tampa, FL, USA. ,
  • Ryan M. Young School of Natural Sciences and Ryan Institute, National University of Ireland Galway, H91 TK33 Galway, Republic of Ireland. ,
  • Fiona L. Kearns Department of Chemistry, University of South Florida, Tampa, FL, USA. ,
  • Tracess Smalley Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute; Tampa, FL, USA. ,
  • Jennifer M. Binning Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute; Tampa, FL, USA. ,
  • John P. Dalton Molecular Parasitology Laboratory (MPL), Centre for One Health and Ryan Institute, School of Natural Science, National University of Ireland Galway, Galway, Republic of Ireland. ,
  • Mark P. Johnson School of Natural Sciences and Ryan Institute, National University of Ireland Galway, H91 TK33 Galway, Republic of Ireland. ,
  • H. Lee Woodcock Department of Chemistry, University of South Florida, Tampa, FL, USA. ,
  • A. Louise Allcock School of Natural Sciences and Ryan Institute, National University of Ireland Galway, H91 TK33 Galway, Republic of Ireland. ,
  • Bill J. Baker Department of Chemistry, University of South Florida, Tampa, FL, USA.

Abstract

Cold water benthic environments are a prolific source of structurally diverse molecules with a range of bioactivities against human disease. Specimens of a previously chemically unexplored soft coral, Duva florida, were collected during a deep-sea cruise that sampled marine invertebrates along the Irish continental margin in 2018. Tuaimenal A (1), a cyclized merosesquiterpenoid representing a new carbon scaffold with a highly substituted chromene core, was discovered through exploration of the soft coral secondary metabolome via NMR-guided fractionation. The absolute stereochemistry was determined through vibrational circular dichroism. Functional biochemical assays and in silico docking experiments found tuaimenal A selectively inhibits the viral main protease (3CLpro) of SARS-CoV-2.

Version notes

Tuaimenal A not only demonstrates in silico activity, but also demonstrates inhibition in biochemical assays against the 3CLpro enzyme of SARS-CoV-2 and this has been included. The antiproliferative activity has been removed.

Content

Thumbnail image of 20220510_ChemRxiv_tuaimenalA.pdf

Supplementary material

Thumbnail image of 20220501_JNP_SI_tuaimenalA_revised.pdf
Supplementary Information for Tuaimenal A
The following Supporting Information is available: 1H, 13C, 2D NMR, HRESIMS, UV, FTIR spectra, and VCD data for tuaimenal A (1); binding site residues for rigid docking with 3CLpro, Plpro, RdRp, and TMPRSS2 protein targets (PDF).