Tuaimenal A, a meroterpene from the Irish deep-sea soft coral Drifa sp., displays antiviral and antiproliferative bioactivity.

Cold water benthic environments are a prolific source of structurally diverse molecules with a range of bioactivity against human disease. Specimens of a previously chemically unexplored soft coral, Drifa sp., 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. Absolute stereochemistry was determined through vibrational circular dichroism. Functional assays and in silico docking experiments found tuaimenal A active against two major health burdens: SARS-CoV-2 and cancer. Biochemical and cell-based assays established that tuaimenal A effectively and selectively inhibits the viral main protease (3CLpro) and mitigates proliferation of cervical cancer cells lines. Given the need for novel treatment options for both diseases, our data suggest that tuaimenal A and/or its derivates could culminate in the development of a unique and effective drug.