Receptor recognition is the first step of viral infection and is a key determinant of host cell and tissue tropism. Enhanced binding affinity between SARS-CoV S and hACE2 was proposed to correlate with increased virus transmissibility and disease severity in humans. Indeed, SARS-CoV isolates from the three phases of the 2002-2003 epidemic were more efficiently transmitted among humans and more pathogenic than the isolates associated with 2003-2004 re-emergence that caused only a few cases, in line with their binding affinities for hACE2.