A “second life” for ACE2 was discovered in 2003, when a novel respiratory infective disease, known as severe acute respiratory syndrome (SARS), appeared in China and spread all over Asia and Canada, with a lethality rate of 10% (Rota et al., 2003). The responsible pathogen was identified in a positive strand RNA virus belonging to the coronavirus family and named SARS-CoV (Ksiazek et al., 2003). The virus genome was sequenced and this allowed the identification of the spike glycoprotein (S), whose N-terminal portion, or S1-domain, was found to mediate the high affinity binding to host cells (Marra et al., 2003). The group of Farzan et al. succeeded in identifying the cell receptor: they showed that SARS-CoV efficiently infected African Monkey kidney cell line Vero E6 and co-immunoprecipitated a glycoprotein responsible for virus binding and entry, which was identified as ACE2 (Li et al., 2003).