evidence: Viral fusion. The fusion process that is mediated by S protein of SARS-CoV is similar to that mediated by class I viral fusion proteins of other viruses, such as HIV-1 and murine hepatitis virus (MHV)53,54, but may occur in the acidic environment of the endosomes, rather than on the cell surface. S2 contains heptad repeat 1 (HR1) and HR2 domains, which play an important part in SARS-CoV fusion with target cells. Binding of the RBD of S1 to the receptor ACE2 triggers a conformational change of the S2 from a pre-fusion form to a post-fusion form, resulting in insertion of the putative fusion peptide (amino acids 770–788)31 into the target cell membrane and association of HR1 and HR2 domains to form a six-helix bundle fusion core structure. This brings the viral envelope and target cell membrane into close proximity for fusion. The crystal structure of the SARS-CoV fusion core is described in detail in ref. 55 (Fig. 3). Similarly to the S protein of MHV, but not gp41 of HIV-1, SARS-CoV S protein has a longer HR1 region than HR2 region.