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

We extended our SARS-CoV-2 inhibitor studies on alotaketal C (a sesterterpenoid previously discovered in extracts of the marine sponge Phorbas sp. collected in Howe Sound, British Columbia) to explore the proposed host-directed ACE2 shedding antiviral mechanism of action. We synthesized two analogs of alotaketal C, which were one order of magnitude more potent in inhibiting the infection of Calu3 cells with Omicron CoV-2-BA.1 and Omicron CoV-2-BA.5., and thereby identified potential pan-SARS-CoV-2 drug candidates. The Jean Lab’s contribution to this study in Organic Letters was fully supported by our CoVaRR-Net grant.

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