A SARS-coronovirus 3CL protease inhibitor isolated from the marine sponge Axinella cf. corrugata: structure elucidation and synthesis

Two coumarin derivatives, esculetin-4-carboxylic acid methyl ester (1) and esculetin-4-carboxylic acid ethyl ester (2), have been isolated from the marine sponge Axinella cf. corrugata. Structure determination included analysis of spectroscopic data and total synthesis of compound 2. These are the first coumarin derivatives isolated from a marine sponge. The ethyl ester 2 was found to be an in vitro inhibitor of SARS 3CL-protease and an effective inhibitor of SARS-CoV replication in Vero cells at non-cytotoxic concentrations.