Synthetic Analogs of the Sponge Sesterterpenoid Alotaketal C are Potent Inhibitors of SARS-CoV‑2 Omicron BA.1 and BA.5 Infections of Human Lung Cells

The protein kinase C-activating sponge natural product alotaketal C () potently inhibits the infection of human Calu-3 lung cells by SARS-CoV-2 Omicron BA.1 and BA.5 variants. Simplified analogs of have been synthesized and tested for anti-SARS-CoV-2 activity providing SAR data for the antiviral pharmacophore of . Analogs and , which are missing the C-11 substituents in and have modified C-13 appendages, are ∼2- to 7-fold more potent than and have equal or larger selectivity indices.